Abstract
Metabolic disorders, whether hereditary or acquired, affect the brain, and abnormalities of the brain are related to cellular integrity; particularly in regard to neurons and astrocytes as well as interactions between them. Metabolic disturbances lead to alterations in cellular function as well as microscopic and macroscopic structural changes in the brain with diabetes, the most typical example of metabolic disorders, and a number of hereditary metabolic disorders. Alternatively, cellular dysfunction and degeneration of the brain lead to metabolic disturbances in hereditary neurological disorders with neurodegeneration. Nuclear magnetic resonance (NMR) techniques allow us to assess a range of pathophysiological changes of the brain in vivo. For example, magnetic resonance spectroscopy detects alterations in brain metabolism and energetics. Physiological magnetic resonance imaging (MRI) detects accompanying changes in cerebral blood flow related to neurovascular coupling. Diffusion and T1/T2-weighted MRI detect microscopic and macroscopic changes of the brain structure. This review summarizes current NMR findings of functional, physiological and biochemical alterations within a number of hereditary and acquired metabolic disorders in both animal models and humans. The global view of the impact of these metabolic disorders on the brain may be useful in identifying the unique and/or general patterns of abnormalities in the living brain related to the pathophysiology of the diseases, and identifying future fields of inquiry.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- AChE:
-
Acetylcholinesterase
- ADC:
-
Apparent diffusion coefficient
- GABA:
-
γ-Aminobutyric acid
- AA:
-
Arachidonic acid
- BBB:
-
Blood brain barrier
- CBF:
-
Cerebral blood flow
- Cho:
-
Choline
- Cr:
-
Creatine
- CoA:
-
Coenzyme A
- Cr:
-
Creatine
- CK:
-
Creatine kinase
- DWI:
-
Diffusion weighted imaging
- EETs:
-
Epoxyeicosatrienoic acids
- Glu:
-
Glutamate
- Gln:
-
Glutamine
- Glx:
-
Glutamate + glutamine
- GSH:
-
Glutathione
- GSD I:
-
Glycogen storage disease type I
- GSD II:
-
Glycogen storage disease type II
- GM:
-
Gray matter
- GDP:
-
Guanosine diphosphate
- GTP:
-
Guanosine triphosphate
- HD:
-
Huntington disease
- 20-HETE:
-
20-Hydroxyeicosatetraenoic acid
- LDH:
-
Lactate dehydrogenase
- T1:
-
Longitudinal relaxation time
- MRI:
-
Magnetic resonance imaging
- MRS:
-
Magnetic resonance spectroscopy
- MELAS:
-
Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes
- MCTs:
-
Monocarboxylate transporters
- NMR:
-
Nuclear magnetic resonance
- NAA:
-
N-Acetylaspartate
- OAA:
-
Oxaloacetate
- PCr:
-
Phosphocreatine
- PGE2 :
-
Prostaglandin E2
- PDH:
-
Pyruvate dehydrogenase complex
- T2:
-
Transverse relaxation time
- T1DM:
-
Type 1 diabetes mellitus
- T2DM:
-
Type 2 diabetes mellitus
- WM:
-
White matter
References
Maragakis NJ, Rothstein JD (2006) Mechanisms of Disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol 2:679–689
Allen NJ, Barres BA (2009) Neuroscience: glia—more than just brain glue. Nature 457:675–677
Bristol LA, Rothstein JD (1996) Glutamate transporter gene expression in amyotrophic lateral sclerosis motor cortex. Ann Neurol 39:676–679
Bruijn LI, Becher MW, Lee MK, Anderson KL, Jenkins NA, Copeland NG et al (1997) ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron 18:327–338
Howland DS, Liu J, She Y, Goad B, Maragakis NJ, Kim B et al (2002) Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc Natl Acad Sci USA 99:1604–1609
Wisniewski HM, Wegiel J (1991) Spatial relationships between astrocytes and classical plaque components. Neurobiol Aging 12:593–600
Feany MB, Dickson DW (1995) Widespread cytoskeletal pathology characterizes corticobasal degeneration. Am J Pathol 146:1388–1396
Nagele RG, Wegiel J, Venkataraman V, Imaki H, Wang KC, Wegiel J (2004) Contribution of glial cells to the development of amyloid plaques in Alzheimer’s disease. Neurobiol Aging 25:663–674
DeWitt DA, Perry G, Cohen M, Doller C, Silver J (1998) Astrocytes regulate microglial phagocytosis of senile plaque cores of Alzheimer’s disease. Exp Neurol 149:329–340
Lievens JC, Woodman B, Mahal A, Spasic-Boscovic O, Samuel D, Kerkerian-Le Goff L et al (2001) Impaired glutamate uptake in the R6 Huntington’s disease transgenic mice. Neurobiol Dis 8:807–821
Behrens PF, Franz P, Woodman B, Lindenberg KS, Landwehrmeyer GB (2002) Impaired glutamate transport and glutamate-glutamine cycling: downstream effects of the Huntington mutation. Brain 125:1908–1922
Singhrao SK, Thomas P, Wood JD, MacMillan JC, Neal JW, Harper PS et al (1998) Huntingtin protein colocalizes with lesions of neurodegenerative diseases: an investigation in Huntington’s, Alzheimer’s, and Pick’s diseases. Exp Neurol 150:213–222
Damier P, Hirsch EC, Zhang P, Agid Y, Javoy-Agid F (1993) Glutathione peroxidase, glial cells and Parkinson’s disease. Neuroscience 52:1–6
Teismann P, Schulz JB (2004) Cellular pathology of Parkinson’s disease: astrocytes, microglia and inflammation. Cell Tissue Res 318:149–161
Forno LS, DeLanney LE, Irwin I, Di Monte D, Langston JW (1992) Astrocytes and Parkinson’s disease. Prog Brain Res 94:429–436
Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A (2001) Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 27:117–120
Yang Y, Higashimori H, Morel L (2013) Developmental maturation of astrocytes and pathogenesis of neurodevelopmental disorders. J Neurodev Disord 5:22
Lebon V, Petersen KF, Cline GW, Shen J, Mason GF, Dufour S et al (2002) Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J Neurosci 22:1523–1531
Freeman MR, Doherty J (2006) Glial cell biology in Drosophila and vertebrates. Trends Neurosci 29:82–90
Jones EV, Bouvier DS (2014) Astrocyte-secreted matricellular proteins in CNS remodelling during development and disease. Neural Plast 2014:321209
Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140:918–934
Belanger M, Magistretti PJ (2009) The role of astroglia in neuroprotection. Dialogues Clin Neurosci 11:281–295
Waniewski RA, Martin DL (1986) Exogenous glutamate is metabolized to glutamine and exported by rat primary astrocyte cultures. J Neurochem 47:304–313
Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW et al (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–686
Allen NJ, Barres BA (2005) Signaling between glia and neurons: focus on synaptic plasticity. Curr Opin Neurobiol 15:542–548
Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN et al (1999) Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 23:297–308
Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6:626–640
Khowaja A, Choi IY, Seaquist ER, Oz G (2015) In vivo magnetic resonance spectroscopy of cerebral glycogen metabolism in animals and humans. Metab Brain Dis 30:255–261
Seifert G, Schilling K, Steinhauser C (2006) Astrocyte dysfunction in neurological disorders: a molecular perspective. Nat Rev Neurosci 7:194–206
Suarez I, Bodega G, Fernandez B (2002) Glutamine synthetase in brain: effect of ammonia. Neurochem Int 41:123–142
Dringen R, Hirrlinger J (2003) Glutathione pathways in the brain. Biol Chem 384:505–516
Howarth C (2014) The contribution of astrocytes to the regulation of cerebral blood flow. Front Neurosci 8:103
Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA (2010) Glial and neuronal control of brain blood flow. Nature 468:232–243
Pfeuffer J, Tkac I, Provencher SW, Gruetter R (1999) Toward an in vivo neurochemical profile: quantification of 18 metabolites in short-echo-time (1)H NMR spectra of the rat brain. J Magn Reson 141:104–120
Tkac I, Henry PG, Andersen P, Keene CD, Low WC, Gruetter R (2004) Highly resolved in vivo 1H NMR spectroscopy of the mouse brain at 9.4 T. Magn Reson Med 52:478–484
Mlynarik V, Cudalbu C, Xin L, Gruetter R (2008) 1H NMR spectroscopy of rat brain in vivo at 14.1Tesla: improvements in quantification of the neurochemical profile. J Magn Reson 194:163–168
Mountford CE, Stanwell P, Lin A, Ramadan S, Ross B (2010) Neurospectroscopy: the past, present and future. Chem Rev 110:3060–3086
Rae CD (2014) A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra. Neurochem Res 39:1–36
Basser PJ (1995) Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed 8:333–344
Basser PJ, Mattiello J, LeBihan D (1994) MR diffusion tensor spectroscopy and imaging. Biophys J 66:259–267
Detre JA, Leigh JS, Williams DS, Koretsky AP (1992) Perfusion imaging. Magn Reson Med 23:37–45
Kim SG (1995) Quantification of relative cerebral blood flow change by flow-sensitive alternating inversion recovery (FAIR) technique: application to functional mapping. Magn Reson Med 34:293–301
Kwong KK, Chesler DA, Weisskoff RM, Donahue KM, Davis TL, Ostergaard L et al (1995) MR perfusion studies with T1-weighted echo planar imaging. Magn Reson Med 34:878–887
Villringer A, Rosen BR, Belliveau JW, Ackerman JL, Lauffer RB, Buxton RB et al (1988) Dynamic imaging with lanthanide chelates in normal brain: contrast due to magnetic susceptibility effects. Magn Reson Med 6:164–174
Rosen BR, Belliveau JW, Vevea JM, Brady TJ (1990) Perfusion imaging with NMR contrast agents. Magn Reson Med 14:249–265
Geissler A, Frund R, Scholmerich J, Feuerbach S, Zietz B (2003) Alterations of cerebral metabolism in patients with diabetes mellitus studied by proton magnetic resonance spectroscopy. Exp Clin Endocrinol Diabetes 111:421–427
Makimattila S, Malmberg-Ceder K, Hakkinen AM, Vuori K, Salonen O, Summanen P et al (2004) Brain metabolic alterations in patients with type 1 diabetes-hyperglycemia-induced injury. J Cereb Blood Flow Metab 24:1393–1399
Jongen C, van der Grond J, Kappelle LJ, Biessels GJ, Viergever MA, Pluim JP (2007) Automated measurement of brain and white matter lesion volume in type 2 diabetes mellitus. Diabetologia 50:1509–1516
Janson J, Laedtke T, Parisi JE, O’Brien P, Petersen RC, Butler PC (2004) Increased risk of type 2 diabetes in Alzheimer disease. Diabetes 53:474–481
Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553
Triplitt C, Solis-Herrera C, Reasner C, DeFronzo RA, Cersosimo E (2000) Classification of diabetes mellitus. In: De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, Hershman JM et al (eds) Endotext. MDText.com Inc, South Dartmouth (MA)
Wang WT, Lee P, Yeh HW, Smirnova IV, Choi IY (2012) Effects of acute and chronic hyperglycemia on the neurochemical profiles in the rat brain with streptozotocin-induced diabetes detected using in vivo (1)H MR spectroscopy at 9.4 T. J Neurochem 121:407–417
Wang N, Zhao LC, Zheng YQ, Dong MJ, Su Y, Chen WJ et al (2015) Alteration of interaction between astrocytes and neurons in different stages of diabetes: a nuclear magnetic resonance study using [1-(13)C]glucose and [2-(13)C]acetate. Mol Neurobiol 51:843–852
Duarte JM, Carvalho RA, Cunha RA, Gruetter R (2009) Caffeine consumption attenuates neurochemical modifications in the hippocampus of streptozotocin-induced diabetic rats. J Neurochem 111:368–379
Mangia S, Kumar AF, Moheet AA, Roberts RJ, Eberly LE, Seaquist ER et al (2013) Neurochemical profile of patients with type 1 diabetes measured by (1)H-MRS at 4 T. J Cereb Blood Flow Metab 33:754–759
Northam EA, Rankins D, Lin A, Wellard RM, Pell GS, Finch SJ et al (2009) Central nervous system function in youth with type 1 diabetes 12 years after disease onset. Diabetes Care 32:445–450
Sarac K, Akinci A, Alkan A, Aslan M, Baysal T, Ozcan C (2005) Brain metabolite changes on proton magnetic resonance spectroscopy in children with poorly controlled type 1 diabetes mellitus. Neuroradiology 47:562–565
De Feyter HM, Mason GF, Shulman GI, Rothman DL, Petersen KF (2013) Increased brain lactate concentrations without increased lactate oxidation during hypoglycemia in type 1 diabetic individuals. Diabetes 62:3075–3080
van de Ven KC, van der Graaf M, Tack CJ, Heerschap A, de Galan BE (2012) Steady-state brain glucose concentrations during hypoglycemia in healthy humans and patients with type 1 diabetes. Diabetes 61:1974–1977
Seaquist ER, Tkac I, Damberg G, Thomas W, Gruetter R (2005) Brain glucose concentrations in poorly controlled diabetes mellitus as measured by high-field magnetic resonance spectroscopy. Metabolism 54:1008–1013
Criego AB, Tkac I, Kumar A, Thomas W, Gruetter R, Seaquist ER (2005) Brain glucose concentrations in patients with type 1 diabetes and hypoglycemia unawareness. J Neurosci Res 79:42–47
Donath MY, Shoelson SE (2011) Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 11:98–107
Brundel M, Kappelle LJ, Biessels GJ (2014) Brain imaging in type 2 diabetes. Eur Neuropsychopharmacol 24:1967–1981
van der Graaf M, Janssen SW, van Asten JJ, Hermus AR, Sweep CG, Pikkemaat JA et al (2004) Metabolic profile of the hippocampus of Zucker diabetic fatty rats assessed by in vivo 1H magnetic resonance spectroscopy. NMR Biomed 17:405–410
Ajilore O, Haroon E, Kumaran S, Darwin C, Binesh N, Mintz J et al (2007) Measurement of brain metabolites in patients with type 2 diabetes and major depression using proton magnetic resonance spectroscopy. Neuropsychopharmacology 32:1224–1231
Sahin I, Alkan A, Keskin L, Cikim A, Karakas HM, Firat AK et al (2008) Evaluation of in vivo cerebral metabolism on proton magnetic resonance spectroscopy in patients with impaired glucose tolerance and type 2 diabetes mellitus. J Diabetes Complicat 22:254–260
Kreis R, Ross BD (1992) Cerebral metabolic disturbances in patients with subacute and chronic diabetes mellitus: detection with proton MR spectroscopy. Radiology 184:123–130
Kario K, Ishikawa J, Hoshide S, Matsui Y, Morinari M, Eguchi K et al (2005) Diabetic brain damage in hypertension: role of renin-angiotensin system. Hypertension 45:887–893
Tiehuis A, van der Meer F, Mali W, Pleizier M, Biessels GJ, Kappelle J et al (2010) MR spectroscopy of cerebral white matter in type 2 diabetes; no association with clinical variables and cognitive performance. Neuroradiology 52:155–161
Mak CM, Lee HC, Chan AY, Lam CW (2013) Inborn errors of metabolism and expanded newborn screening: review and update. Crit Rev Clin Lab Sci 50:142–162
Sahoo S, Franzson L, Jonsson JJ, Thiele I (2012) A compendium of inborn errors of metabolism mapped onto the human metabolic network. Mol BioSyst 8:2545–2558
Sedel F (2013) Inborn errors of metabolism in adult neurology. Rev Neurol (Paris) 169(Suppl 1):S63–S69
Ibrahim M, Parmar HA, Hoefling N, Srinivasan A (2014) Inborn errors of metabolism: combining clinical and radiologic clues to solve the mystery. AJR Am J Roentgenol 203:W315–W327
Blau N, van Spronsen FJ, Levy HL (2010) Phenylketonuria. Lancet 376:1417–1427
Lindegren ML, Krishnaswami S, Fonnesbeck C et al (2012) Adjuvant treatment for phenylketonuria (PKU). Agency for Healthcare Research and Quality, Rockville
Okano Y, Nagasaka H (2013) Optimal serum phenylalanine for adult patients with phenylketonuria. Mol Genet Metab 110:424–430
Pietz J, Kreis R, Rupp A, Mayatepek E, Rating D, Boesch C et al (1999) Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria. J Clin Invest 103:1169–1178
Hoeksma M, Reijngoud DJ, Pruim J, de Valk HW, Paans AM, van Spronsen FJ (2009) Phenylketonuria: high plasma phenylalanine decreases cerebral protein synthesis. Mol Genet Metab 96:177–182
De Graaf RA (2007) In vivo NMR spectroscopy: principles and techniques. Wiley, Chichester
Anderson PJ, Leuzzi V (2010) White matter pathology in phenylketonuria. Mol Genet Metab 99(Suppl 1):S3–S9
Liang L, Gu X, Lu L, Li D, Zhang X (2011) Phenylketonuria-related synaptic changes in a BTBR-Pah(enu2) mouse model. NeuroReport 22:617–622
Leuzzi V, Tosetti M, Montanaro D, Carducci C, Artiola C, Carducci C et al (2007) The pathogenesis of the white matter abnormalities in phenylketonuria. A multimodal 3.0 tesla MRI and magnetic resonance spectroscopy (1H MRS) study. J Inherit Metab Dis 30:209–216
Scarabino T, Popolizio T, Tosetti M, Montanaro D, Giannatempo GM, Terlizzi R et al (2009) Phenylketonuria: white-matter changes assessed by 3.0-T magnetic resonance (MR) imaging, MR spectroscopy and MR diffusion. Radiol Med 114:461–474
Sener RN (2003) Phenylketonuria: diffusion magnetic resonance imaging and proton magnetic resonance spectroscopy. J Comput Assist Tomogr 27:541–543
Avison MJ, Herschkowitz N, Novotny EJ, Petroff OA, Rothman DL, Colombo JP et al (1990) Proton NMR observation of phenylalanine and an aromatic metabolite in the rabbit brain in vivo. Pediatr Res 27:566–570
Moller HE, Weglage J, Bick U, Wiedermann D, Feldmann R, Ullrich K (2003) Brain imaging and proton magnetic resonance spectroscopy in patients with phenylketonuria. Pediatrics 112:1580–1583
Pietz J, Kreis R, Boesch C, Penzien J, Rating D, Herschkowitz N (1995) The dynamics of brain concentrations of phenylalanine and its clinical significance in patients with phenylketonuria determined by in vivo 1H magnetic resonance spectroscopy. Pediatr Res 38:657–663
Pietz J, Lutz T, Zwygart K, Hoffmann GF, Ebinger F, Boesch C et al (2003) Phenylalanine can be detected in brain tissue of healthy subjects by 1H magnetic resonance spectroscopy. J Inherit Metab Dis 26:683–692
de Groot MJ, Sijens PE, Reijngoud DJ, Paans AM, van Spronsen FJ (2015) Phenylketonuria: brain phenylalanine concentrations relate inversely to cerebral protein synthesis. J Cereb Blood Flow Metab 35:200–205
Koch R, Burton B, Hoganson G, Peterson R, Rhead W, Rouse B et al (2002) Phenylketonuria in adulthood: a collaborative study. J Inherit Metab Dis 25:333–346
Weglage J, Wiedermann D, Denecke J, Feldmann R, Koch HG, Ullrich K et al (2002) Individual blood-brain barrier phenylalanine transport in siblings with classical phenylketonuria. J Inherit Metab Dis 25:431–436
Sitta A, Ribas GS, Mescka CP, Barschak AG, Wajner M, Vargas CR (2014) Neurological damage in MSUD: the role of oxidative stress. Cell Mol Neurobiol 34:157–165
Chuang JL, Chuang DT (2000) Diagnosis and mutational analysis of maple syrup urine disease using cell cultures. Methods Enzymol 324:413–423
Pessoa-Pureur R, Wajner M (2007) Cytoskeleton as a potential target in the neuropathology of maple syrup urine disease: insight from animal studies. J Inherit Metab Dis 30:664–672
Felber SR, Sperl W, Chemelli A, Murr C, Wendel U (1993) Maple syrup urine disease: metabolic decompensation monitored by proton magnetic resonance imaging and spectroscopy. Ann Neurol 33:396–401
Muelly ER, Moore GJ, Bunce SC, Mack J, Bigler DC, Morton DH et al (2013) Biochemical correlates of neuropsychiatric illness in maple syrup urine disease. J Clin Invest 123:1809–1820
Sgaravatti AM, Rosa RB, Schuck PF, Ribeiro CA, Wannmacher CM, Wyse AT et al (2003) Inhibition of brain energy metabolism by the alpha-keto acids accumulating in maple syrup urine disease. Biochim Biophys Acta 1639:232–238
Nakamura K, Matsumoto S, Mitsubuchi H, Endo F (2015) Diagnosis and treatment of hereditary tyrosinemia in Japan. Pediatr Int 57:37–40
Macedo LG, Carvalho-Silva M, Ferreira GK, Vieira JS, Olegario N, Goncalves RC et al (2013) Effect of acute administration of l-tyrosine on oxidative stress parameters in brain of young rats. Neurochem Res 38:2625–2630
Ferreira GK, Carvalho-Silva M, Gomes LM, Scaini G, Teixeira LJ, Mota IT et al (2015) The characterization of neuroenergetic effects of chronic l-tyrosine administration in young rats: evidence for striatal susceptibility. Metab Brain Dis 30:215–221
Sener RN (2005) Tyrosinemia: computed tomography, magnetic resonance imaging, diffusion magnetic resonance imaging, and proton spectroscopy findings in the brain. J Comput Assist Tomogr 29:323–325
Marsden D (2014) The organic acidemias. In: Murray MF, Babyatsky MW, Giovanni MA, Alkuraya FS, Stewart DR (eds) Clinical genomics: practical applications in adult patient care. McGraw-Hill Education, New York
Cohn RM, Roth KS (2004) Hyperammonemia, bane of the brain. Clin Pediatr (Phila) 43:683–689
Kanaumi T, Takashima S, Hirose S, Kodama T, Iwasaki H (2006) Neuropathology of methylmalonic acidemia in a child. Pediatr Neurol 34:156–159
Chandler RJ, Zerfas PM, Shanske S, Sloan J, Hoffmann V, DiMauro S et al (2009) Mitochondrial dysfunction in mut methylmalonic acidemia. FASEB J 23:1252–1261
Trinh BC, Melhem ER, Barker PB (2001) Multi-slice proton MR spectroscopy and diffusion-weighted imaging in methylmalonic acidemia: report of two cases and review of the literature. Am J Neuroradiol 22:831–833
Takeuchi M, Harada M, Matsuzaki K, Hisaoka S, Nishitani H, Mori K (2003) Magnetic resonance imaging and spectroscopy in a patient with treated methylmalonic acidemia. J Comput Assist Tomogr 27:547–551
Schreiber J, Chapman KA, Summar ML, Ah Mew N, Sutton VR, MacLeod E et al (2012) Neurologic considerations in propionic acidemia. Mol Genet Metab 105:10–15
Hamilton RL, Haas RH, Nyhan WL, Powell HC, Grafe MR (1995) Neuropathology of propionic acidemia: a report of two patients with basal ganglia lesions. J Child Neurol 10:25–30
Feliz B, Witt DR, Harris BT (2003) Propionic acidemia: a neuropathology case report and review of prior cases. Arch Pathol Lab Med 127:e325–e328
Bergman AJ, Van der Knaap MS, Smeitink JA, Duran M, Dorland L, Valk J et al (1996) Magnetic resonance imaging and spectroscopy of the brain in propionic acidemia: clinical and biochemical considerations. Pediatr Res 40:404–409
Davison JE, Davies NP, Wilson M, Sun Y, Chakrapani A, McKiernan PJ et al (2011) MR spectroscopy-based brain metabolite profiling in propionic acidaemia: metabolic changes in the basal ganglia during acute decompensation and effect of liver transplantation. Orphanet J Rare Dis 6:19
Sen A, Pillay RS (2011) Striatal necrosis in type 1 glutaric aciduria: different stages in two siblings. J Pediatr Neurosci 6:146–148
Hou LC, Veeravagu A, Hsu AR, Enns GM, Huhn SL (2007) Glutaric acidemia type I: a neurosurgical perspective. Report of two cases. J Neurosurg 107:167–172
Bjugstad KB, Goodman SI, Freed CR (2000) Age at symptom onset predicts severity of motor impairment and clinical outcome of glutaric acidemia type 1. J Pediatr 137:681–686
Koeller DM, Woontner M, Crnic LS, Kleinschmidt-DeMasters B, Stephens J, Hunt EL et al (2002) Biochemical, pathologic and behavioral analysis of a mouse model of glutaric acidemia type I. Hum Mol Genet 11:347–357
Zinnanti WJ, Lazovic J, Housman C, LaNoue K, O’Callaghan JP, Simpson I et al (2007) Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I. J Clin Invest 117:3258–3270
Quincozes-Santos A, Rosa RB, Leipnitz G, de Souza DF, Seminotti B, Wajner M et al (2010) Induction of S100B secretion in C6 astroglial cells by the major metabolites accumulating in glutaric acidemia type I. Metab Brain Dis 25:191–198
Kurtcan S, Aksu B, Alkan A, Guler S, Iscan A (2015) MRS features during encephalopathic crisis period in 11 years old case with GA-1. Brain Dev 37:546–551
Sijens PE, Smit GP, Meiners LC, Oudkerk M, van Spronsen FJ (2006) Cerebral 1H MR spectroscopy revealing white matter NAA decreases in glutaric aciduria type I. Mol Genet Metab 88:285–289
Oguz KK, Ozturk A, Cila A (2005) Diffusion-weighted MR imaging and MR spectroscopy in glutaric aciduria type 1. Neuroradiology 47:229–234
Kurul S, Cakmakci H, Dirik E (2004) Glutaric aciduria type 1: proton magnetic resonance spectroscopy findings. Pediatr Neurol 31:228–231
Lamp J, Keyser B, Koeller DM, Ullrich K, Braulke T, Muhlhausen C (2011) Glutaric aciduria type 1 metabolites impair the succinate transport from astrocytic to neuronal cells. J Biol Chem 286:17777–17784
Wortmann SB, Kluijtmans LA, Engelke UF, Wevers RA, Morava E (2012) The 3-methylglutaconic acidurias: what’s new? J Inherit Metab Dis 35:13–22
Engelke UF, Kremer B, Kluijtmans LA, van der Graaf M, Morava E, Loupatty FJ et al (2006) NMR spectroscopic studies on the late onset form of 3-methylglutaconic aciduria type I and other defects in leucine metabolism. NMR Biomed 19:271–278
Ensenauer R, Muller CB, Schwab KO, Gibson KM, Brandis M, Lehnert W (2000) 3-Methylglutaconyl-CoA hydratase deficiency: a new patient with speech retardation as the leading sign. J Inherit Metab Dis 23:341–344
Wortmann SB, Kremer BH, Graham A, Willemsen MA, Loupatty FJ, Hogg SL et al (2010) 3-Methylglutaconic aciduria type I redefined: a syndrome with late-onset leukoencephalopathy. Neurology 75:1079–1083
Matsumori M, Shoji Y, Takahashi T, Shoji Y, Takada G (2005) A molecular lesion in a Japanese patient with severe phenotype of 3-methylglutaconic aciduria type I. Pediatr Int 47:684–686
Al-Essa M, Bakheet S, Al-Shamsan L, Patay Z, Powe J, Ozand PT (1999) 18Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in type IV 3-methylglutaconic aciduria: clinical and MRI correlations. Brain Dev 21:24–29
Leipnitz G, Seminotti B, Amaral AU, de Bortoli G, Solano A, Schuck PF et al (2008) Induction of oxidative stress by the metabolites accumulating in 3-methylglutaconic aciduria in cerebral cortex of young rats. Life Sci 82:652–662
Scurrell E, Davies E, Baines E, Cherubini GB, Platt S, Blakemore W et al (2008) Neuropathological findings in a Staffordshire bull terrier with l-2-hydroxyglutaric aciduria. J Comp Pathol 138:160–164
Liang D, Bhatta S, Gerzanich V, Simard JM (2007) Cytotoxic edema: mechanisms of pathological cell swelling. Neurosurg Focus 22:E2
Seijo-Martinez M, Navarro C, Castro del Rio M, Vila O, Puig M, Ribes A et al (2005) l-2-hydroxyglutaric aciduria: clinical, neuroimaging, and neuropathological findings. Arch Neurol 62:666–670
Sener RN (2003) l-2 hydroxyglutaric aciduria: proton magnetic resonance spectroscopy and diffusion magnetic resonance imaging findings. J Comput Assist Tomogr 27:38–43
Aydin K, Ozmen M, Tatli B, Sencer S (2003) Single-voxel MR spectroscopy and diffusion-weighted MRI in two patients with l-2-hydroxyglutaric aciduria. Pediatr Radiol 33:872–876
Read MH, Bonamy C, Laloum D, Belloy F, Constans JM, Guillois B et al (2005) Clinical, biochemical, magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS) findings in a fourth case of combined d- and l-2 hydroxyglutaric aciduria. J Inherit Metab Dis 28:1149–1150
Gropman AL, Fricke ST, Seltzer RR, Hailu A, Adeyemo A, Sawyer A et al (2008) 1H MRS identifies symptomatic and asymptomatic subjects with partial ornithine transcarbamylase deficiency. Mol Genet Metab 95:21–30
Sprouse C, King J, Helman G, Pacheco-Colon I, Shattuck K, Breeden A et al (2014) Investigating neurological deficits in carriers and affected patients with ornithine transcarbamylase deficiency. Mol Genet Metab 113:136–141
Desjardins P, Du T, Jiang W, Peng L, Butterworth RF (2012) Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure: role of glutamine redefined. Neurochem Int 60:690–696
Takanashi J, Barkovich AJ, Cheng SF, Kostiner D, Baker JC, Packman S (2003) Brain MR imaging in acute hyperammonemic encephalopathy arising from late-onset ornithine transcarbamylase deficiency. Am J Neuroradiol 24:390–393
Bireley WR, Van Hove JL, Gallagher RC, Fenton LZ (2012) Urea cycle disorders: brain MRI and neurological outcome. Pediatr Radiol 42:455–462
Thakur V, Rupar CA, Ramsay DA, Singh R, Fraser DD (2006) Fatal cerebral edema from late-onset ornithine transcarbamylase deficiency in a juvenile male patient receiving valproic acid. Pediatr Crit Care Med 7:273–276
Lichter-Konecki U, Mangin JM, Gordish-Dressman H, Hoffman EP, Gallo V (2008) Gene expression profiling of astrocytes from hyperammonemic mice reveals altered pathways for water and potassium homeostasis in vivo. Glia 56:365–377
Norenberg MD (1996) Astrocytic-ammonia interactions in hepatic encephalopathy. Semin Liver Dis 16:245–253
Takahashi H, Koehler RC, Brusilow SW, Traystman RJ (1991) Inhibition of brain glutamine accumulation prevents cerebral edema in hyperammonemic rats. Am J Physiol 261:H825–H829
Gropman A (2010) Brain imaging in urea cycle disorders. Mol Genet Metab 100(Suppl 1):S20–S30
Takanashi J, Kurihara A, Tomita M, Kanazawa M, Yamamoto S, Morita F et al (2002) Distinctly abnormal brain metabolism in late-onset ornithine transcarbamylase deficiency. Neurology 59:210–214
Connelly A, Cross JH, Gadian DG, Hunter JV, Kirkham FJ, Leonard JV (1993) Magnetic resonance spectroscopy shows increased brain glutamine in ornithine carbamoyl transferase deficiency. Pediatr Res 33:77–81
Albrecht J, Norenberg MD (2006) Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology 44:788–794
Ruder J, Legacy J, Russo G, Davis R (2014) Neonatal citrullinemia: novel, reversible neuroimaging findings correlated with ammonia level changes. Pediatr Neurol 51:553–556
Kara B, Albayram S, Tutar O, Altun G, Kocer N, Islak C (2009) Diffusion-weighted magnetic resonance imaging findings of a patient with neonatal citrullinemia during acute episode. Eur J Paediatr Neurol 13:280–282
Majoie CB, Mourmans JM, Akkerman EM, Duran M, Poll-The BT (2004) Neonatal citrullinemia: comparison of conventional MR, diffusion-weighted, and diffusion tensor findings. Am J Neuroradiol 25:32–35
Oshiro S, Kochinda T, Tana T, Yamazato M, Kobayashi K, Komine Y et al (2002) A patient with adult-onset type II citrullinemia on long-term hemodialysis: reversal of clinical symptoms and brain MRI findings. Am J Kidney Dis 39:189–192
Wong YC, Au WL, Xu M, Ye J, Lim CC (2007) Magnetic resonance spectroscopy in adult-onset citrullinemia: elevated glutamine levels in comatose patients. Arch Neurol 64:1034–1037
Choi CG, Yoo HW (2001) Localized proton MR spectroscopy in infants with urea cycle defect. Am J Neuroradiol 22:834–837
Braissant O (2010) Current concepts in the pathogenesis of urea cycle disorders. Mol Genet Metab 100(Suppl 1):S3–S12
Neufeld EF, Muenzer J (2014) The mucopolysaccharidoses. In: Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson KM et al (eds) The online metabolic and molecular bases of inherited disease. McGraw-Hill, New York
Jumbo-Lucioni P, Parkinson W, Broadie K (2014) Overelaborated synaptic architecture and reduced synaptomatrix glycosylation in a Drosophila classic galactosemia disease model. Dis Model Mech 7:1365–1378
Timson DJ (2014) Purple sweet potato colour–a potential therapy for galactosemia? Int J Food Sci Nutr 65:391–393
Nelson MD Jr, Wolff JA, Cross CA, Donnell GN, Kaufman FR (1992) Galactosemia: evaluation with MR imaging. Radiology 184:255–261
Moller HE, Ullrich K, Vermathen P, Schuierer G, Koch HG (1995) In vivo study of brain metabolism in galactosemia by 1H and 31P magnetic resonance spectroscopy. Eur J Pediatr 154:S8–S13
Otaduy MC, Leite CC, Lacerda MT, Costa MO, Arita F, Prado E et al (2006) Proton MR spectroscopy and imaging of a galactosemic patient before and after dietary treatment. AJNR Am J Neuroradiol 27:204–207
Cakmakci H, Pekcevik Y, Yis U, Unalp A, Kurul S (2010) Diagnostic value of proton MR spectroscopy and diffusion-weighted MR imaging in childhood inherited neurometabolic brain diseases and review of the literature. Eur J Radiol 74:e161–e171
Wehrli SL, Reynolds R, Chen J, Yager C, Segal S (2002) Metabolism of 13C galactose by lymphoblasts from patients with galactosemia determined by NMR spectroscopy. Mol Genet Metab 77:296–303
Tsakiris S, Marinou K, Schulpis KH (2002) The effect of galactose metabolic disorders on rat brain Na+, K+-ATPase activity. Z Naturforsch C 57:939–943
Bell JE, Hume R, Busuttil A, Burchell A (1993) Immunocytochemical detection of the microsomal glucose-6-phosphatase in human brain astrocytes. Neuropathol Appl Neurobiol 19:429–435
Gotoh J, Itoh Y, Kuang TY, Cook M, Law MJ, Sokoloff L (2000) Negligible glucose-6-phosphatase activity in cultured astroglia. J Neurochem 74:1400–1408
Dienel GA, Nelson T, Cruz NF, Jay T, Crane AM, Sokoloff L (1988) Over-estimation of glucose-6-phosphatase activity in brain in vivo. Apparent difference in rates of [2–3H]glucose and [U-14C]glucose utilization is due to contamination of precursor pool with 14C-labeled products and incomplete recovery of 14C-labeled metabolites. J Biol Chem 263:19697–19708
Nelson T, Lucignani G, Atlas S, Crane AM, Dienel GA, Sokoloff L (1985) Reexamination of glucose-6-phosphatase activity in the brain in vivo: no evidence for a futile cycle. Science 229:60–62
Santos BL, de Souza CF, Schuler-Faccini L, Refosco L, Epifanio M, Nalin T et al (2014) Glycogen storage disease type I: clinical and laboratory profile. J Pediatr (Rio J) 90:572–579
Melis D, Parenti G, Della Casa R, Sibilio M, Romano A, Di Salle F et al (2004) Brain damage in glycogen storage disease type I. J Pediatr 144:637–642
Weghuber D, Mandl M, Krssak M, Roden M, Nowotny P, Brehm A et al (2007) Characterization of hepatic and brain metabolism in young adults with glycogen storage disease type 1: a magnetic resonance spectroscopy study. Am J Physiol Endocrinol Metab 293:E1378–E1384
Di Rocco M, Buzzi D, Taro M (2007) Glycogen storage disease type II: clinical overview. Acta Myol 26:42–44
Chen CP, Lin SP, Tzen CY, Tsai FJ, Hwu WL, Wang W (2004) Detection of a homozygous D645E mutation of the acid alpha-glucosidase gene and glycogen deposition in tissues in a second-trimester fetus with infantile glycogen storage disease type II. Prenat Diagn 24:231–232
Teng YT, Su WJ, Hou JW, Huang SF (2004) Infantile-onset glycogen storage disease type II (Pompe disease): report of a case with genetic diagnosis and pathological findings. Chang Gung Med J 27:379–384
Sidman RL, Taksir T, Fidler J, Zhao M, Dodge JC, Passini MA et al (2008) Temporal neuropathologic and behavioral phenotype of 6neo/6neo Pompe disease mice. J Neuropathol Exp Neurol 67:803–818
Chien YH, Lee NC, Peng SF, Hwu WL (2006) Brain development in infantile-onset Pompe disease treated by enzyme replacement therapy. Pediatr Res 60:349–352
Lee CC, Chen CY, Chou TY, Chen FH, Lee CC, Zimmerman RA (1996) Cerebral MR manifestations of Pompe disease in an infant. Am J Neuroradiol 17:321–322
Burrow TA, Bailey LA, Kinnett DG, Hopkin RJ (2010) Acute progression of neuromuscular findings in infantile Pompe disease. Pediatr Neurol 42:455–458
Vafai SB, Mootha VK (2012) Mitochondrial disorders as windows into an ancient organelle. Nature 491:374–383
Hertz L, Peng L, Dienel GA (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 27:219–249
Roe CR, Mochel F (2006) Anaplerotic diet therapy in inherited metabolic disease: therapeutic potential. J Inherit Metab Dis 29:332–340
Mochel F, DeLonlay P, Touati G, Brunengraber H, Kinman RP, Rabier D et al (2005) Pyruvate carboxylase deficiency: clinical and biochemical response to anaplerotic diet therapy. Mol Genet Metab 84:305–312
Breen C, White FJ, Scott CA, Heptinstall L, Walter JH, Jones SA et al (2014) Unsuccessful treatment of severe pyruvate carboxylase deficiency with triheptanoin. Eur J Pediatr 173:361–366
Pineda M, Campistol J, Vilaseca MA, Briones P, Ribes A, Temudo T et al (1995) An atypical French form of pyruvate carboxylase deficiency. Brain Dev 17:276–279
Garcia-Cazorla A, Rabier D, Touati G, Chadefaux-Vekemans B, Marsac C, de Lonlay P et al (2006) Pyruvate carboxylase deficiency: metabolic characteristics and new neurological aspects. Ann Neurol 59:121–127
Ahmad A, Kahler SG, Kishnani PS, Artigas-Lopez M, Pappu AS, Steiner R et al (1999) Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate. Am J Med Genet 87:331–338
Ortez C, Jou C, Cortes-Saladelafont E, Moreno J, Perez A, Ormazabal A et al (2013) Infantile parkinsonism and GABAergic hypotransmission in a patient with pyruvate carboxylase deficiency. Gene 532:302–306
Patel KP, O’Brien TW, Subramony SH, Shuster J, Stacpoole PW (2012) The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab 106:385–394
Imbard A, Boutron A, Vequaud C, Zater M, de Lonlay P, de Baulny HO et al (2011) Molecular characterization of 82 patients with pyruvate dehydrogenase complex deficiency. Structural implications of novel amino acid substitutions in E1 protein. Mol Genet Metab 104:507–516
Barnerias C, Saudubray JM, Touati G, De Lonlay P, Dulac O, Ponsot G et al (2010) Pyruvate dehydrogenase complex deficiency: four neurological phenotypes with differing pathogenesis. Dev Med Child Neurol 52:e1–e9
Zand DJ, Simon EM, Pulitzer SB, Wang DJ, Wang ZJ, Rorke LB et al (2003) In vivo pyruvate detected by MR spectroscopy in neonatal pyruvate dehydrogenase deficiency. Am J Neuroradiol 24:1471–1474
Wada N, Matsuishi T, Nonaka M, Naito E, Yoshino M (2004) Pyruvate dehydrogenase E1alpha subunit deficiency in a female patient: evidence of antenatal origin of brain damage and possible etiology of infantile spasms. Brain Dev 26:57–60
Shevell MI, Matthews PM, Scriver CR, Brown RM, Otero LJ, Legris M et al (1994) Cerebral dysgenesis and lactic acidemia: an MRI/MRS phenotype associated with pyruvate dehydrogenase deficiency. Pediatr Neurol 11:224–229
Dey R, Mine M, Desguerre I, Slama A, Van Den Berghe L, Brivet M et al (2003) A new case of pyruvate dehydrogenase deficiency due to a novel mutation in the PDX1 gene. Ann Neurol 53:273–277
Soares-Fernandes JP, Teixeira-Gomes R, Cruz R, Ribeiro M, Magalhaes Z, Rocha JF et al (2008) Neonatal pyruvate dehydrogenase deficiency due to a R302H mutation in the PDHA1 gene: MRI findings. Pediatr Radiol 38:559–562
Pliss L, Mazurchuk R, Spernyak JA, Patel MS (2007) Brain MR imaging and proton MR spectroscopy in female mice with pyruvate dehydrogenase complex deficiency. Neurochem Res 32:645–654
Rubio-Gozalbo ME, Heerschap A, Trijbels JM, De Meirleir L, Thijssen HO, Smeitink JA (1999) Proton MR spectroscopy in a child with pyruvate dehydrogenase complex deficiency. Magn Reson Imaging 17:939–944
Harada M, Tanouchi M, Arai K, Nishitani H, Miyoshi H, Hashimoto T (1996) Therapeutic efficacy of a case of pyruvate dehydrogenase complex deficiency monitored by localized proton magnetic resonance spectroscopy. Magn Reson Imaging 14:129–133
Whitehouse S, Cooper RH, Randle PJ (1974) Mechanism of activation of pyruvate dehydrogenase by dichloroacetate and other halogenated carboxylic acids. Biochem J 141:761–774
Bowker-Kinley MM, Davis WI, Wu P, Harris RA, Popov KM (1998) Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. Biochem J 329(Pt 1):191–196
Tanji K, Vu TH, Schon EA, DiMauro S, Bonilla E (1999) Kearns–Sayre syndrome: unusual pattern of expression of subunits of the respiratory chain in the cerebellar system. Ann Neurol 45:377–383
Heidenreich JO, Klopstock T, Schirmer T, Saemann P, Mueller-Felber W, Auer DP (2006) Chronic progressive external ophthalmoplegia: MR spectroscopy and MR diffusion studies in the brain. Am J Roentgenol 187:820–824
Schiffmann R, van der Knaap MS (2009) Invited article: an MRI-based approach to the diagnosis of white matter disorders. Neurology 72:750–759
Chu BC, Terae S, Takahashi C, Kikuchi Y, Miyasaka K, Abe S et al (1999) MRI of the brain in the Kearns–Sayre syndrome: report of four cases and a review. Neuroradiology 41:759–764
Serrano M, Garcia-Silva MT, Martin-Hernandez E, O’Callaghan Mdel M, Quijada P, Martinez-Aragon A et al (2010) Kearns–Sayre syndrome: cerebral folate deficiency, MRI findings and new cerebrospinal fluid biochemical features. Mitochondrion 10:429–432
Mathews PM, Andermann F, Silver K, Karpati G, Arnold DL (1993) Proton MR spectroscopic characterization of differences in regional brain metabolic abnormalities in mitochondrial encephalomyopathies. Neurology 43:2484–2490
Kuwabara T, Watanabe H, Tanaka K, Tsuji S, Ohkubo M, Ito T et al (1994) Mitochondrial encephalomyopathy: elevated visual cortex lactate unresponsive to photic stimulation–a localized 1H-MRS study. Neurology 44:557–559
Choi C, Sunwoo IN, Kim HS, Kim DI (2000) Transient improvement of pyruvate metabolism after coenzyme Q therapy in Kearns–Sayre syndrome: MRS study. Yonsei Med J 41:676–679
Kapeller P, Fazekas F, Offenbacher H, Stollberger R, Schmidt R, Bergloff J et al (1996) Magnetic resonance imaging and spectroscopy of progressive cerebral involvement in Kearns–Sayre syndrome. J Neurol Sci 135:126–130
Yokoyama T, Hasegawa K, Obama R, Ishihara T, Yagishita S (2010) MELAS with diffuse degeneration of the cerebral white matter: report of an autopsy case. Neuropathology 30:56–60
Lee SK, Kim J, Kim HD, Lee JS, Lee YM (2010) Initial experiences with proton MR spectroscopy in treatment monitoring of mitochondrial encephalopathy. Yonsei Med J 51:672–675
Tsuchiya K, Miyazaki H, Akabane H, Yamamoto M, Kondo H, Mizusawa H et al (1999) MELAS with prominent white matter gliosis and atrophy of the cerebellar granular layer: a clinical, genetic, and pathological study. Acta Neuropathol 97:520–524
Oppenheim C, Galanaud D, Samson Y, Sahel M, Dormont D, Wechsler B et al (2000) Can diffusion weighted magnetic resonance imaging help differentiate stroke from stroke-like events in MELAS? J Neurol Neurosurg Psychiatry 69:248–250
Pauli W, Zarzycki A, Krzysztalowski A, Walecka A (2013) CT and MRI imaging of the brain in MELAS syndrome. Pol J Radiol 78:61–65
Kolb SJ, Costello F, Lee AG, White M, Wong S, Schwartz ED et al (2003) Distinguishing ischemic stroke from the stroke-like lesions of MELAS using apparent diffusion coefficient mapping. J Neurol Sci 216:11–15
Alemdar M, Iseri P, Selekler M, Budak F, Demirci A, Komsuoglu SS (2007) MELAS presented with status epilepticus and Anton–Babinski syndrome; value of ADC mapping in MELAS. J Neuropsychiatry Clin Neurosci 19:482–483
Kim JH, Lim MK, Jeon TY, Rha JH, Eo H, Yoo SY et al (2011) Diffusion and perfusion characteristics of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode) in thirteen patients. Korean J Radiol 12:15–24
Stoquart-Elsankari S, Lehmann P, Perin B, Gondry-Jouet C, Godefroy O (2008) MRI and diffusion-weighted imaging followup of a stroke-like event in a patient with MELAS. J Neurol 255:1593–1595
Moller HE, Kurlemann G, Putzler M, Wiedermann D, Hilbich T, Fiedler B (2005) Magnetic resonance spectroscopy in patients with MELAS. J Neurol Sci 229–230:131–139
Kamada K, Takeuchi F, Houkin K, Kitagawa M, Kuriki S, Ogata A et al (2001) Reversible brain dysfunction in MELAS: MEG, and (1)H MRS analysis. J Neurol Neurosurg Psychiatry 70:675–678
Casimiro C, Martins J, Nunes C, Parreira T, Batista S, Cordeiro M et al (2012) Conventional and diffusion-weighted magnetic resonance imaging and proton spectroscopy in MELAS. Acta Med Port 25(Suppl 1):59–64
Barry DS, O’Keeffe GW (2013) Peroxisomes: the neuropathological consequences of peroxisomal dysfunction in the developing brain. Int J Biochem Cell Biol 45:2012–2015
Fernandes J, Saudubray JM, Van den Berghe G (1995) Inborn metabolic diseases: diagnosis and treatment. Springer, Berlin
Rahim RS, Meedeniya AC, Crane DI (2014) Central serotonergic neuron deficiency in a mouse model of Zellweger syndrome. Neuroscience 274:229–241
Ezgu F, Eminoglu T, Okur I, Gunduz M, Tumer L, Hasanoglu A et al (2011) An infantile case of Zellweger syndrome presented with Kabuki-like phenotype. Genet Couns 22:217–220
Lee PR, Raymond GV (2013) Child neurology: Zellweger syndrome. Neurology 80:e207–e210
Crane DI (2014) Revisiting the neuropathogenesis of Zellweger syndrome. Neurochem Int 69:1–8
Kingsley PB, Shah TC, Woldenberg R (2006) Identification of diffuse and focal brain lesions by clinical magnetic resonance spectroscopy. NMR Biomed 19:435–462
Weller S, Rosewich H, Gartner J (2008) Cerebral MRI as a valuable diagnostic tool in Zellweger spectrum patients. J Inherit Metab Dis 31:270–280
Barth PG, Majoie CB, Gootjes J, Wanders RJ, Waterham HR, van der Knaap MS et al (2004) Neuroimaging of peroxisome biogenesis disorders (Zellweger spectrum) with prolonged survival. Neurology 62:439–444
van der Knaap MS, Vermeulen G, Barkhof F, Hart AA, Loeber JG, Weel JF (2004) Pattern of white matter abnormalities at MR imaging: use of polymerase chain reaction testing of Guthrie cards to link pattern with congenital cytomegalovirus infection. Radiology 230:529–536
Groenendaal F, Bianchi MC, Battini R, Tosetti M, Boldrini A, de Vries LS et al (2001) Proton magnetic resonance spectroscopy (1H-MRS) of the cerebrum in two young infants with Zellweger syndrome. Neuropediatrics 32:23–27
Kruska N, Schonfeld P, Pujol A, Reiser G (2015) Astrocytes and mitochondria from adrenoleukodystrophy protein (ABCD1)-deficient mice reveal that the adrenoleukodystrophy-associated very long-chain fatty acids target several cellular energy-dependent functions. Biochim Biophys Acta 1852:925–936
Engelen M, Kemp S, Poll-The BT (2014) X-linked adrenoleukodystrophy: pathogenesis and treatment. Curr Neurol Neurosci Rep 14:486
Hein S, Schonfeld P, Kahlert S, Reiser G (2008) Toxic effects of X-linked adrenoleukodystrophy-associated, very long chain fatty acids on glial cells and neurons from rat hippocampus in culture. Hum Mol Genet 17:1750–1761
Kumar AJ, Kohler W, Kruse B, Naidu S, Bergin A, Edwin D et al (1995) MR findings in adult-onset adrenoleukodystrophy. Am J Neuroradiol 16:1227–1237
Fatemi A, Barker PB, Ulug AM, Nagae-Poetscher LM, Beauchamp NJ, Moser AB et al (2003) MRI and proton MRSI in women heterozygous for X-linked adrenoleukodystrophy. Neurology 60:1301–1307
Dubey P, Fatemi A, Barker PB, Degaonkar M, Troeger M, Zackowski K et al (2005) Spectroscopic evidence of cerebral axonopathy in patients with “pure” adrenomyeloneuropathy. Neurology 64:304–310
Oz G, Tkac I, Charnas LR, Choi IY, Bjoraker KJ, Shapiro EG et al (2005) Assessment of adrenoleukodystrophy lesions by high field MRS in non-sedated pediatric patients. Neurology 64:434–441
Eichler FS, Itoh R, Barker PB, Mori S, Garrett ES, van Zijl PC et al (2002) Proton MR spectroscopic and diffusion tensor brain MR imaging in X-linked adrenoleukodystrophy: initial experience. Radiology 225:245–252
Torvik A, Torp S, Kase BF, Ek J, Skjeldal O, Stokke O (1988) Infantile Refsum’s disease: a generalized peroxisomal disorder. Case report with postmortem examination. J Neurol Sci 85:39–53
Ferdinandusse S, Zomer AW, Komen JC, van den Brink CE, Thanos M, Hamers FP et al (2008) Ataxia with loss of Purkinje cells in a mouse model for Refsum disease. Proc Natl Acad Sci USA 105:17712–17717
Ronicke S, Kruska N, Kahlert S, Reiser G (2009) The influence of the branched-chain fatty acids pristanic acid and Refsum disease-associated phytanic acid on mitochondrial functions and calcium regulation of hippocampal neurons, astrocytes, and oligodendrocytes. Neurobiol Dis 36:401–410
Ruether K, Baldwin E, Casteels M, Feher MD, Horn M, Kuranoff S et al (2010) Adult Refsum disease: a form of tapetoretinal dystrophy accessible to therapy. Surv Ophthalmol 55:531–538
Choksi V, Hoeffner E, Karaarslan E, Yalcinkaya C, Cakirer S (2003) Infantile refsum disease: case report. Am J Neuroradiol 24:2082–2084
Cakirer S, Savas MR (2005) Infantile Refsum disease: serial evaluation with MRI. Pediatr Radiol 35:212–215
Ghosh A, Jana M, Modi K, Gonzalez FJ, Sims KB, Berry-Kravis E et al (2015) Activation of peroxisome proliferator-activated receptor alpha induces lysosomal biogenesis in brain cells: implications for lysosomal storage disorders. J Biol Chem 290:10309–10324
Walkley SU (1998) Cellular pathology of lysosomal storage disorders. Brain Pathol 8:175–193
Lachman R, Martin KW, Castro S, Basto MA, Adams A, Teles EL (2010) Radiologic and neuroradiologic findings in the mucopolysaccharidoses. J Pediatr Rehabil Med 3:109–118
Wraith JE, Jones S (2014) Mucopolysaccharidosis type I. Pediatr Endocrinol Rev 12(Suppl 1):102–106
Hinderer C, Bell P, Gurda BL, Wang Q, Louboutin JP, Zhu Y et al (2014) Liver-directed gene therapy corrects cardiovascular lesions in feline mucopolysaccharidosis type I. Proc Natl Acad Sci USA 111:14894–14899
Wilkinson FL, Holley RJ, Langford-Smith KJ, Badrinath S, Liao A, Langford-Smith A et al (2012) Neuropathology in mouse models of mucopolysaccharidosis type I. IIIA and IIIB. PLoS ONE 7:e35787
Vite CH, Nestrasil I, Mlikotic A, Jens JK, Snella EM, Gross W et al (2013) Features of brain MRI in dogs with treated and untreated mucopolysaccharidosis type I. Comp Med 63:163–173
Kulkarni MV, Williams JC, Yeakley JW, Andrews JL, McArdle CB, Narayana PA et al (1987) Magnetic resonance imaging in the diagnosis of the cranio-cervical manifestations of the mucopolysaccharidoses. Magn Reson Imaging 5:317–323
Murata R, Nakajima S, Tanaka A, Miyagi N, Matsuoka O, Kogame S et al (1989) MR imaging of the brain in patients with mucopolysaccharidosis. Am J Neuroradiol 10:1165–1170
Davison JE, Hendriksz CJ, Sun Y, Davies NP, Gissen P, Peet AC (2010) Quantitative in vivo brain magnetic resonance spectroscopic monitoring of neurological involvement in mucopolysaccharidosis type II (Hunter syndrome). J Inherit Metab Dis 33(Suppl 3):S395–S399
Parsons VJ, Hughes DG, Wraith JE (1996) Magnetic resonance imaging of the brain, neck and cervical spine in mild Hunter’s syndrome (mucopolysaccharidoses type II). Clin Radiol 51:719–723
Vedolin L, Schwartz IV, Komlos M, Schuch A, Puga AC, Pinto LL et al (2007) Correlation of MR imaging and MR spectroscopy findings with cognitive impairment in mucopolysaccharidosis II. Am J Neuroradiol 28:1029–1033
Gilkes JA, Heldermon CD (2014) Mucopolysaccharidosis III (Sanfilippo Syndrome)- disease presentation and experimental therapies. Pediatr Endocrinol Rev 12(Suppl 1):133–140
Valstar MJ, Ruijter GJ, van Diggelen OP, Poorthuis BJ, Wijburg FA (2008) Sanfilippo syndrome: a mini-review. J Inherit Metab Dis 31:240–252
Concolino D, Muzzi G, Pisaturo L, Piccirillo A, Di Natale P, Strisciuglio P (2008) Precocious puberty in Sanfilippo IIIA disease: diagnosis and follow-up of two new cases. Eur J Med Genet 51:466–471
Barone R, Nigro F, Triulzi F, Musumeci S, Fiumara A, Pavone L (1999) Clinical and neuroradiological follow-up in mucopolysaccharidosis type III (Sanfilippo syndrome). Neuropediatrics 30:270–274
Lee C, Dineen TE, Brack M, Kirsch JE, Runge VM (1993) The mucopolysaccharidoses: characterization by cranial MR imaging. Am J Neuroradiol 14:1285–1292
Chedrawi AK, Al-Hassnan ZN, Al-Muhaizea M, Colak D, Al-Younes B, Albakheet A et al (2012) Novel V97G ASAH1 mutation found in Farber disease patients: unique appearance of the disease with an intermediate severity, and marked early involvement of central and peripheral nervous system. Brain Dev 34:400–404
Levade T, Moser HW, Fensom AH, Harzer K, Moser AB, Salvayre R (1995) Neurodegenerative course in ceramidase deficiency (Farber disease) correlates with the residual lysosomal ceramide turnover in cultured living patient cells. J Neurol Sci 134:108–114
Bar J, Linke T, Ferlinz K, Neumann U, Schuchman EH, Sandhoff K (2001) Molecular analysis of acid ceramidase deficiency in patients with Farber disease. Hum Mutat 17:199–209
Ehlert K, Frosch M, Fehse N, Zander A, Roth J, Vormoor J (2007) Farber disease: clinical presentation, pathogenesis and a new approach to treatment. Pediatr Rheumatol Online J 5:15
Brunetti-Pierri N, Scaglia F (2008) GM1 gangliosidosis: review of clinical, molecular, and therapeutic aspects. Mol Genet Metab 94:391–396
Kaye EM, Alroy J, Raghavan SS, Schwarting GA, Adelman LS, Runge V et al (1992) Dysmyelinogenesis in animal model of GM1 gangliosidosis. Pediatr Neurol 8:255–261
Murnane RD, Wright RW Jr, Ahern-Rindell AJ, Prieur DJ (1991) Prenatal lesions in an ovine fetus with GM1 gangliosidosis. Am J Med Genet 39:106–111
Gururaj A, Sztriha L, Hertecant J, Johansen JG, Georgiou T, Campos Y et al (2005) Magnetic resonance imaging findings and novel mutations in GM1 gangliosidosis. J Child Neurol 20:57–60
Chen CY, Zimmerman RA, Lee CC, Chen FH, Yuh YS, Hsiao HS (1998) Neuroimaging findings in late infantile GM1 gangliosidosis. Am J Neuroradiol 19:1628–1630
Sharma S, Sankhyan N, Kabra M, Gulati S (2010) Teaching neuroimages: T2 hypointense thalami in infantile GM1 gangliosidosis. Neurology 74:e47
Brunetti-Pierri N, Bhattacharjee MB, Wang ZJ, Zili C, Wenger DA, Potocki L et al (2008) Brain proton magnetic resonance spectroscopy and neuromuscular pathology in a patient with GM1 gangliosidosis. J Child Neurol 23:73–78
Erol I, Alehan F, Pourbagher MA, Canan O, Vefa Yildirim S (2006) Neuroimaging findings in infantile GM1 gangliosidosis. Eur J Paediatr Neurol 10:245–248
De Grandis E, Di Rocco M, Pessagno A, Veneselli E, Rossi A (2009) MR imaging findings in 2 cases of late infantile GM1 gangliosidosis. Am J Neuroradiol 30:1325–1327
Tuteja M, Bidchol AM, Girisha KM, Phadke S (2015) White matter changes in GM1 gangliosidosis. Indian Pediatr 52:155–156
Lowe JP, Stuckey DJ, Awan FR, Jeyakumar M, Neville DC, Platt FM et al (2005) MRS reveals additional hexose N-acetyl resonances in the brain of a mouse model for Sandhoff disease. NMR Biomed 18:517–526
Myerowitz R, Lawson D, Mizukami H, Mi Y, Tifft CJ, Proia RL (2002) Molecular pathophysiology in Tay–Sachs and Sandhoff diseases as revealed by gene expression profiling. Hum Mol Genet 11:1343–1350
Cachon-Gonzalez MB, Wang SZ, Ziegler R, Cheng SH, Cox TM (2014) Reversibility of neuropathology in Tay–Sachs-related diseases. Hum Mol Genet 23:730–748
Huang JQ, Trasler JM, Igdoura S, Michaud J, Hanal N, Gravel RA (1997) Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay–Sachs and Sandhoff diseases. Hum Mol Genet 6:1879–1885
Grosso S, Farnetani MA, Berardi R, Margollicci M, Galluzzi P, Vivarelli R et al (2003) GM2 gangliosidosis variant B1 neuroradiological findings. J Neurol 250:17–21
Aydin K, Bakir B, Tatli B, Terzibasioglu E, Ozmen M (2005) Proton MR spectroscopy in three children with Tay–Sachs disease. Pediatr Radiol 35:1081–1085
Imamura A, Miyajima H, Ito R, Orii KO (2008) Serial MR imaging and 1H-MR spectroscopy in monozygotic twins with Tay–Sachs disease. Neuropediatrics 39:259–263
Wilken B, Dechent P, Hanefeld F, Frahm J (2008) Proton MRS of a child with Sandhoff disease reveals elevated brain hexosamine. Eur J Paediatr Neurol 12:56–60
Felderhoff-Mueser U, Sperner J, Konstanzcak P, Navon R, Weschke B (2001) 31Phosphorus magnetic resonance spectroscopy in late-onset Tay–Sachs disease. J Child Neurol 16:377–380
Wada R, Tifft CJ, Proia RL (2000) Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation. Proc Natl Acad Sci USA 97:10954–10959
Albrecht J, Dellani PR, Muller MJ, Schermuly I, Beck M, Stoeter P et al (2007) Voxel based analyses of diffusion tensor imaging in Fabry disease. J Neurol Neurosurg Psychiatry 78:964–969
Fellgiebel A, Gartenschlager M, Wildberger K, Scheurich A, Desnick RJ, Sims K (2014) Enzyme replacement therapy stabilized white matter lesion progression in fabry disease. Cerebrovasc Dis 38:448–456
Fellgiebel A, Muller MJ, Mazanek M, Baron K, Beck M, Stoeter P (2005) White matter lesion severity in male and female patients with Fabry disease. Neurology 65:600–602
Kaye EM, Kolodny EH, Logigian EL, Ullman MD (1988) Nervous system involvement in Fabry’s disease: clinicopathological and biochemical correlation. Ann Neurol 23:505–509
Cabrera-Salazar MA, O’Rourke E, Charria-Ortiz G, Barranger JA (2005) Radiological evidence of early cerebral microvascular disease in young children with Fabry disease. J Pediatr 147:102–105
Moore DF, Altarescu G, Barker WC, Patronas NJ, Herscovitch P, Schiffmann R (2003) White matter lesions in Fabry disease occur in ‘prior’ selectively hypometabolic and hyperperfused brain regions. Brain Res Bull 62:231–240
Marino S, Borsini W, Buchner S, Mortilla M, Stromillo ML, Battaglini M et al (2006) Diffuse structural and metabolic brain changes in Fabry disease. J Neurol 253:434–440
Gavazzi C, Borsini W, Guerrini L, Della Nave R, Rocca MA, Tessa C et al (2006) Subcortical damage and cortical functional changes in men and women with Fabry disease: a multifaceted MR study. Radiology 241:492–500
Jardim L, Vedolin L, Schwartz IV, Burin MG, Cecchin C, Kalakun L et al (2004) CNS involvement in Fabry disease: clinical and imaging studies before and after 12 months of enzyme replacement therapy. J Inherit Metab Dis 27:229–240
Mercimek-Mahmutoglu S, Gruber S, Rolfs A, Stadlbauer A, Woeber C, Kurnik P et al (2007) Neurological and brain MRS findings in patients with Gaucher disease type 1. Mol Genet Metab 91:390–395
Weiss K, Gonzalez AN, Lopez G, Pedoeim L, Groden C, Sidransky E (2015) The clinical management of Type 2 Gaucher disease. Mol Genet Metab 114:110–122
Baris HN, Cohen IJ, Mistry PK (2014) Gaucher disease: the metabolic defect, pathophysiology, phenotypes and natural history. Pediatr Endocrinol Rev 12(Suppl 1):72–81
Vitner EB, Dekel H, Zigdon H, Shachar T, Farfel-Becker T, Eilam R et al (2010) Altered expression and distribution of cathepsins in neuronopathic forms of Gaucher disease and in other sphingolipidoses. Hum Mol Genet 19:3583–3590
Abdel Razek AA, Abd El-Gaber N, Abdalla A, Fathy A, Azab A, Rahman AA (2009) Apparent diffusion coefficient vale of the brain in patients with Gaucher’s disease type II and type III. Neuroradiology 51:773–779
Gruber S, Bogner W, Stadlbauer A, Krssak M, Bodamer O (2011) Magnetic resonance spectroscopy in patients with Fabry and Gaucher disease. Eur J Radiol 79:295–298
Holmay MJ, Terpstra M, Coles LD, Mishra U, Ahlskog M, Oz G et al (2013) N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases. Clin Neuropharmacol 36:103–106
Schuchman EH, McGovern MM, Desnick RJ (2014) Niemann–Pick disease types A and B: acid sphingomyelinase deficiencies. In: Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson KM et al (eds) The online metabolic and molecular bases of inherited disease. McGraw-Hill, New York
Pavlu H, Elleder M (1997) Two novel mutations in patients with atypical phenotypes of acid sphingomyelinase deficiency. J Inherit Metab Dis 20:615–616
Patterson MC, Vanier MT, Suzuki K, Morris JA, Carstea E, Neufeld EB et al (2014) Niemann–Pick disease Type C: a lipid trafficking disorder. In: Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson KM et al (eds) The online metabolic and molecular bases of inherited disease. McGraw-Hill, New York
Burlina A (2014) Niemann–Pick disease type C: introduction and main clinical features. J Neurol 261(Suppl 2):S525–S527
Mengel E, Klunemann HH, Lourenco CM, Hendriksz CJ, Sedel F, Walterfang M et al (2013) Niemann–Pick disease type C symptomatology: an expert-based clinical description. Orphanet J Rare Dis 8:166
Saez PJ, Orellana JA, Vega-Riveros N, Figueroa VA, Hernandez DE, Castro JF et al (2013) Disruption in connexin-based communication is associated with intracellular Ca(2)(+) signal alterations in astrocytes from Niemann–Pick type C mice. PLoS ONE 8:e71361
Baudry M, Yao Y, Simmons D, Liu J, Bi X (2003) Postnatal development of inflammation in a murine model of Niemann–Pick type C disease: immunohistochemical observations of microglia and astroglia. Exp Neurol 184:887–903
Chen G, Li HM, Chen YR, Gu XS, Duan S (2007) Decreased estradiol release from astrocytes contributes to the neurodegeneration in a mouse model of Niemann–Pick disease type C. Glia 55:1509–1518
Sevin M, Lesca G, Baumann N, Millat G, Lyon-Caen O, Vanier MT et al (2007) The adult form of Niemann–Pick disease type C. Brain 130:120–133
Walterfang M, Fahey M, Desmond P, Wood A, Seal ML, Steward C et al (2010) White and gray matter alterations in adults with Niemann–Pick disease type C: a cross-sectional study. Neurology 75:49–56
Trouard TP, Heidenreich RA, Seeger JF, Erickson RP (2005) Diffusion tensor imaging in Niemann–Pick Type C disease. Pediatr Neurol 33:325–330
Lee R, Apkarian K, Jung ES, Yanjanin N, Yoshida S, Mori S et al (2014) Corpus callosum diffusion tensor imaging and volume measures are associated with disease severity in pediatric Niemann–Pick disease type C1. Pediatr Neurol 51(669–674):e665
Totenhagen JW, Yoshimaru ES, Erickson RP, Trouard TP (2013) (1) H magnetic resonance spectroscopy of neurodegeneration in a mouse model of Niemann–Pick type C1 disease. J Magn Reson Imaging 37:1195–1201
Tedeschi G, Bonavita S, Barton NW, Betolino A, Frank JA, Patronas NJ et al (1998) Proton magnetic resonance spectroscopic imaging in the clinical evaluation of patients with Niemann–Pick type C disease. J Neurol Neurosurg Psychiatry 65:72–79
Suzuki K, Suzuki Y (1970) Globoid cell leucodystrophy (Krabbe’s disease): deficiency of galactocerebroside beta-galactosidase. Proc Natl Acad Sci USA 66:302–309
Strasberg P (1986) Cerebrosides and psychosine disrupt mitochondrial functions. Biochem Cell Biol 64:485–489
Abdelhalim AN, Alberico RA, Barczykowski AL, Duffner PK (2014) Patterns of magnetic resonance imaging abnormalities in symptomatic patients with Krabbe disease correspond to phenotype. Pediatr Neurol 50:127–134
Brockmann K, Dechent P, Wilken B, Rusch O, Frahm J, Hanefeld F (2003) Proton MRS profile of cerebral metabolic abnormalities in Krabbe disease. Neurology 60:819–825
Meisingset TW, Ricca A, Neri M, Sonnewald U, Gritti A (2013) Region- and age-dependent alterations of glial-neuronal metabolic interactions correlate with CNS pathology in a mouse model of globoid cell leukodystrophy. J Cereb Blood Flow Metab 33:1127–1137
Luzi P, Rafi MA, Rao HZ, Wenger DA (2013) Sixteen novel mutations in the arylsulfatase A gene causing metachromatic leukodystrophy. Gene 530:323–328
Solders M, Martin DA, Andersson C, Remberger M, Andersson T, Ringden O et al (2014) Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy. Bone Marrow Transplant 49:1046–1051
van Egmond ME, Pouwels PJ, Boelens JJ, Lindemans CA, Barkhof F, Steenwijk MD et al (2013) Improvement of white matter changes on neuroimaging modalities after stem cell transplant in metachromatic leukodystrophy. JAMA Neurol 70:779–782
Gieselmann V, Matzner U, Hess B, Lullmann-Rauch R, Coenen R, Hartmann D et al (1998) Metachromatic leukodystrophy: molecular genetics and an animal model. J Inherit Metab Dis 21:564–574
Kim TS, Kim IO, Kim WS, Choi YS, Lee JY, Kim OW et al (1997) MR of childhood metachromatic leukodystrophy. Am J Neuroradiol 18:733–738
Eichler F, Grodd W, Grant E, Sessa M, Biffi A, Bley A et al (2009) Metachromatic leukodystrophy: a scoring system for brain MR imaging observations. Am J Neuroradiol 30:1893–1897
Groeschel S, Dali C, Clas P, Bohringer J, Duno M, Krarup C et al (2012) Cerebral gray and white matter changes and clinical course in metachromatic leukodystrophy. Neurology 79:1662–1670
Sener RN (2002) Metachromatic leukodystrophy: diffusion MR imaging findings. Am J Neuroradiol 23:1424–1426
Dali C, Hanson LG, Barton NW, Fogh J, Nair N, Lund AM (2010) Brain N-acetylaspartate levels correlate with motor function in metachromatic leukodystrophy. Neurology 75:1896–1903
Martin A, Sevin C, Lazarus C, Bellesme C, Aubourg P, Adamsbaum C (2012) Toward a better understanding of brain lesions during metachromatic leukodystrophy evolution. Am J Neuroradiol 33:1731–1739
Mamourian AC, Hopkin JR, Chawla S, Poptani H (2010) Characteristic MR spectroscopy in fucosidosis: in vitro investigation. Pediatr Radiol 40:1446–1449
Oner AY, Cansu A, Akpek S, Serdaroglu A (2007) Fucosidosis: MRI and MRS findings. Pediatr Radiol 37:1050–1052
Thomas GH (2014) Disorders of glycoprotein degradation: α-mannosidosis, β-mannosidosis, fucosidosis, and sialidosis. In: Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson KM et al (eds) The online metabolic and molecular bases of inherited disease. McGraw-Hill, New York
Willems PJ, Gatti R, Darby JK, Romeo G, Durand P, Dumon JE et al (1991) Fucosidosis revisited: a review of 77 patients. Am J Med Genet 38:111–131
Kondagari GS, Yang J, Taylor RM (2011) Investigation of cerebrocortical and cerebellar pathology in canine fucosidosis and comparison to aged brain. Neurobiol Dis 41:605–613
Jain P, Sharma S, Kumar A, Aneja S (2013) Hypomyelination with T2-hypointense globi pallidi in a child with fucosidosis. J Child Neurol 29:988–989
Borgwardt L, Lund AM, Dali CI (2014) Alpha-mannosidosis—a review of genetic, clinical findings and options of treatment. Pediatr Endocrinol Rev 12(Suppl 1):185–191
Blanz J, Stroobants S, Lullmann-Rauch R, Morelle W, Ludemann M, D’Hooge R et al (2008) Reversal of peripheral and central neural storage and ataxia after recombinant enzyme replacement therapy in alpha-mannosidosis mice. Hum Mol Genet 17:3437–3445
Vite CH, Magnitsky S, Aleman D, O’Donnell P, Cullen K, Ding W et al (2008) Apparent diffusion coefficient reveals gray and white matter disease, and T2 mapping detects white matter disease in the brain in feline alpha-mannosidosis. Am J Neuroradiol 29:308–313
Zoons E, de Koning TJ, Abeling NG, Tijssen MA (2012) Neurodegeneration with brain iron accumulation on MRI: an adult case of alpha-mannosidosis. JIMD Rep 4:99–102
Govender R, Mubaiwa L (2014) Alpha-mannosidosis: a report of 2 siblings and review of the literature. J Child Neurol 29:131–134
Avenarius DF, Svendsen JS, Malm D (2011) Proton nuclear magnetic resonance spectroscopic detection of oligomannosidic n glycans in alpha-mannosidosis: a method of monitoring treatment. J Inherit Metab Dis 34:1023–1027
Alegra T, Koppe T, Acosta A, Sarno M, Burin M, Kessler RG et al (2014) Pitfalls in the prenatal diagnosis of mucolipidosis II alpha/beta: a case report. Meta Gene 2:403–406
Braulke T, Raas-Rothschild A, Kornfeld S (2014) I-cell disease and pseudo-Hurler polydystrophy: disorders of lysosomal enzyme phosphorylation and localization. In: Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson KM et al (eds) The online metabolic and molecular bases of inherited disease. McGraw-Hill, New York
Idol RA, Wozniak DF, Fujiwara H, Yuede CM, Ory DS, Kornfeld S et al (2014) Neurologic abnormalities in mouse models of the lysosomal storage disorders mucolipidosis II and mucolipidosis III gamma. PLoS ONE 9:e109768
Takanashi J, Hayashi M, Yuasa S, Satoh H, Terada H (2012) Hypoyelination in I-cell disease; MRI, MR spectroscopy and neuropathological correlation. Brain Dev 34:780–783
Folkerth RD, Alroy J, Lomakina I, Skutelsky E, Raghavan SS, Kolodny EH (1995) Mucolipidosis IV: morphology and histochemistry of an autopsy case. J Neuropathol Exp Neurol 54:154–164
Grishchuk Y, Sri S, Rudinskiy N, Ma W, Stember KG, Cottle MW et al (2014) Behavioral deficits, early gliosis, dysmyelination and synaptic dysfunction in a mouse model of mucolipidosis IV. Acta Neuropathol Commun 2:133
Micsenyi MC, Dobrenis K, Stephney G, Pickel J, Vanier MT, Slaugenhaupt SA et al (2009) Neuropathology of the Mcoln1(–/–) knockout mouse model of mucolipidosis type IV. J Neuropathol Exp Neurol 68:125–135
Geer JS, Skinner SA, Goldin E, Holden KR (2010) Mucolipidosis type IV: a subtle pediatric neurodegenerative disorder. Pediatr Neurol 42:223–226
Frei KP, Patronas NJ, Crutchfield KE, Altarescu G, Schiffmann R (1998) Mucolipidosis type IV: characteristic MRI findings. Neurology 51:565–569
Bonavita S, Virta A, Jeffries N, Goldin E, Tedeschi G, Schiffmann R (2003) Diffuse neuroaxonal involvement in mucolipidosis IV as assessed by proton magnetic resonance spectroscopic imaging. J Child Neurol 18:443–449
Mercimek-Mahmutoglu S, Stockler-Ipsiroglu S, Salomons GS (1993) Creatine deficiency syndromes. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH et al (eds) GeneReviews(R). University of Washington, Seattle
Stockler S, Schutz PW, Salomons GS (2007) Cerebral creatine deficiency syndromes: clinical aspects, treatment and pathophysiology. Subcell Biochem 46:149–166
Beard E, Braissant O (2010) Synthesis and transport of creatine in the CNS: importance for cerebral functions. J Neurochem 115:297–313
Braissant O, Beard E, Torrent C, Henry H (2010) Dissociation of AGAT, GAMT and SLC6A8 in CNS: relevance to creatine deficiency syndromes. Neurobiol Dis 37:423–433
Gordon N (2010) Guanidinoacetate methyltransferase deficiency (GAMT). Brain Dev 32:79–81
Leuzzi V (2002) Inborn errors of creatine metabolism and epilepsy: clinical features, diagnosis, and treatment. J Child Neurol 17(Suppl 3):3S89–3S97 (discussion 3S97)
Leuzzi V, Bianchi MC, Tosetti M, Carducci C, Cerquiglini CA, Cioni G et al (2000) Brain creatine depletion: guanidinoacetate methyltransferase deficiency (improving with creatine supplementation). Neurology 55:1407–1409
Ganesan V, Johnson A, Connelly A, Eckhardt S, Surtees RA (1997) Guanidinoacetate methyltransferase deficiency: new clinical features. Pediatr Neurol 17:155–157
Stockler S, Hanefeld F (1997) Guanidinoacetate methyltransferase deficiency: a newly recognized inborn error of creatine biosynthesis. Wien Klin Wochenschr 109:86–88
Mercimek-Mahmutoglu S, Salomons GS, Chan A (2014) Case study for the evaluation of current treatment recommendations of guanidinoacetate methyltransferase deficiency: ineffectiveness of sodium benzoate. Pediatr Neurol 51:133–137
Item CB, Stockler-Ipsiroglu S, Stromberger C, Muhl A, Alessandri MG, Bianchi MC et al (2001) Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet 69:1127–1133
Bianchi MC, Tosetti M, Fornai F, Alessandri MG, Cipriani P, De Vito G et al (2000) Reversible brain creatine deficiency in two sisters with normal blood creatine level. Ann Neurol 47:511–513
Nouioua S, Cheillan D, Zaouidi S, Salomons GS, Amedjout N, Kessaci F et al (2013) Creatine deficiency syndrome. A treatable myopathy due to arginine-glycine amidinotransferase (AGAT) deficiency. Neuromuscul Disord 23:670–674
Ndika JD, Johnston K, Barkovich JA, Wirt MD, O’Neill P, Betsalel OT et al (2012) Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine: glycine amidinotransferase deficiency. Mol Genet Metab 106:48–54
Edvardson S, Korman SH, Livne A, Shaag A, Saada A, Nalbandian R et al (2010) l-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation. Mol Genet Metab 101:228–232
Dunbar M, Jaggumantri S, Sargent M, Stockler-Ipsiroglu S, van Karnebeek CD (2014) Treatment of X-linked creatine transporter (SLC6A8) deficiency: systematic review of the literature and three new cases. Mol Genet Metab 112:259–274
Ardon O, Amat di San Filippo C, Salomons GS, Longo N (2010) Creatine transporter deficiency in two half-brothers. Am J Med Genet A 152a:1979–1983
Cecil KM, DeGrauw TJ, Salomons GS, Jakobs C, Egelhoff JC, Clark JF (2003) Magnetic resonance spectroscopy in a 9-day-old heterozygous female child with creatine transporter deficiency. J Comput Assist Tomogr 27:44–47
Mencarelli MA, Tassini M, Pollazzon M, Vivi A, Calderisi M, Falco M et al (2011) Creatine transporter defect diagnosed by proton NMR spectroscopy in males with intellectual disability. Am J Med Genet A 155a:2446–2452
Sosunov AA, Guilfoyle E, Wu X, McKhann GM 2nd, Goldman JE (2013) Phenotypic conversions of “protoplasmic” to “reactive” astrocytes in Alexander disease. J Neurosci 33:7439–7450
Meisingset TW, Risa O, Brenner M, Messing A, Sonnewald U (2010) Alteration of glial-neuronal metabolic interactions in a mouse model of Alexander disease. Glia 58:1228–1234
Bobele GB, Garnica A, Schaefer GB, Leonard JC, Wilson D, Marks WA et al (1990) Neuroimaging findings in Alexander’s disease. J Child Neurol 5:253–258
van der Voorn JP, Pouwels PJ, Salomons GS, Barkhof F, van der Knaap MS (2009) Unraveling pathology in juvenile Alexander disease: serial quantitative MR imaging and spectroscopy of white matter. Neuroradiology 51:669–675
da Silva Pereira CC, Gattas GS, Lucato LT (2013) Alexander disease: a novel mutation in the glial fibrillary acidic protein gene with initial uncommon clinical and magnetic resonance imaging findings. J Comput Assist Tomogr 37:698–700
Nishibayashi F, Kawashima M, Katada Y, Murakami N, Nozaki M (2013) Infantile-onset Alexander disease in a child with long-term follow-up by serial magnetic resonance imaging: a case report. J Med Case Rep 7:194
Graff-Radford J, Schwartz K, Gavrilova RH, Lachance DH, Kumar N (2014) Neuroimaging and clinical features in type II (late-onset) Alexander disease. Neurology 82:49–56
Brockmann K, Dechent P, Meins M, Haupt M, Sperner J, Stephani U et al (2003) Cerebral proton magnetic resonance spectroscopy in infantile Alexander disease. J Neurol 250:300–306
Hoshino H, Kubota M (2014) Canavan disease: clinical features and recent advances in research. Pediatr Int 56:477–483
Janson CG, McPhee SW, Francis J, Shera D, Assadi M, Freese A et al (2006) Natural history of Canavan disease revealed by proton magnetic resonance spectroscopy (1H-MRS) and diffusion-weighted MRI. Neuropediatrics 37:209–221
Kumar S, Sowmyalakshmi R, Daniels SL, Chang R, Surendran S, Matalon R et al (2006) Does ASPA gene mutation in Canavan disease alter oligodendrocyte development? A tissue culture study of ASPA KO mice brain. Adv Exp Med Biol 576:175–182 (discussion 361–173)
Srikanth SG, Chandrashekar HS, Nagarajan K, Jayakumar PN (2007) Restricted diffusion in Canavan disease. Childs Nerv Syst 23:465–468
Sener RN (2003) Canavan disease: diffusion magnetic resonance imaging findings. J Comput Assist Tomogr 27:30–33
Wittsack HJ, Kugel H, Roth B, Heindel W (1996) Quantitative measurements with localized 1H MR spectroscopy in children with Canavan’s disease. J Magn Reson Imaging 6:889–893
Assadi M, Janson C, Wang DJ, Goldfarb O, Suri N, Bilaniuk L et al (2010) Lithium citrate reduces excessive intra-cerebral N-acetyl aspartate in Canavan disease. Eur J Paediatr Neurol 14:354–359
Pacey LK, Xuan IC, Guan S, Sussman D, Henkelman RM, Chen Y et al (2013) Delayed myelination in a mouse model of fragile X syndrome. Hum Mol Genet 22:3920–3930
Peng DX, Kelley RG, Quintin EM, Raman M, Thompson PM, Reiss AL (2014) Cognitive and behavioral correlates of caudate subregion shape variation in fragile X syndrome. Hum Brain Mapp 35:2861–2868
Eliez S, Blasey CM, Freund LS, Hastie T, Reiss AL (2001) Brain anatomy, gender and IQ in children and adolescents with fragile X syndrome. Brain 124:1610–1618
Bray S, Hirt M, Jo B, Hall SS, Lightbody AA, Walter E et al (2011) Aberrant frontal lobe maturation in adolescents with fragile X syndrome is related to delayed cognitive maturation. Biol Psychiatry 70:852–858
Gothelf D, Furfaro JA, Hoeft F, Eckert MA, Hall SS, O’Hara R et al (2008) Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP). Ann Neurol 63:40–51
Kesler SR, Lightbody AA, Reiss AL (2009) Cholinergic dysfunction in fragile X syndrome and potential intervention: a preliminary 1H MRS study. Am J Med Genet A 149a:403–407
Bruno JL, Shelly EW, Quintin EM, Rostami M, Patnaik S, Spielman D et al (2013) Aberrant basal ganglia metabolism in fragile X syndrome: a magnetic resonance spectroscopy study. J Neurodev Disord 5:20
Bossy-Wetzel E, Petrilli A, Knott AB (2008) Mutant huntingtin and mitochondrial dysfunction. Trends Neurosci 31:609–616
Ramos EM, Kovalenko M, Guide JR, St Claire J, Gillis T, Mysore JS et al (2015) Chromosome substitution strain assessment of a Huntington’s disease modifier locus. Mamm Genome 26:119–130
Valenza M, Marullo M, Di Paolo E, Cesana E, Zuccato C, Biella G et al (2015) Disruption of astrocyte-neuron cholesterol cross talk affects neuronal function in Huntington’s disease. Cell Death Differ 22:690–702
Tong X, Ao Y, Faas GC, Nwaobi SE, Xu J, Haustein MD et al (2014) Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington’s disease model mice. Nat Neurosci 17:694–703
Mascalchi M, Lolli F, Della Nave R, Tessa C, Petralli R, Gavazzi C et al (2004) Huntington disease: volumetric, diffusion-weighted, and magnetization transfer MR imaging of brain. Radiology 232:867–873
Aylward EH, Liu D, Nopoulos PC, Ross CA, Pierson RK, Mills JA et al (2012) Striatal volume contributes to the prediction of onset of Huntington disease in incident cases. Biol Psychiatry 71:822–828
Paulsen JS, Langbehn DR, Stout JC, Aylward E, Ross CA, Nance M et al (2008) Detection of Huntington’s disease decades before diagnosis: the Predict-HD study. J Neurol Neurosurg Psychiatry 79:874–880
Tabrizi SJ, Scahill RI, Owen G, Durr A, Leavitt BR, Roos RA et al (2013) Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington’s disease in the TRACK-HD study: analysis of 36-month observational data. Lancet Neurol 12:637–649
Rosas HD, Salat DH, Lee SY, Zaleta AK, Pappu V, Fischl B et al (2008) Cerebral cortex and the clinical expression of Huntington’s disease: complexity and heterogeneity. Brain 131:1057–1068
Hobbs NZ, Henley SM, Ridgway GR, Wild EJ, Barker RA, Scahill RI et al (2010) The progression of regional atrophy in premanifest and early Huntington’s disease: a longitudinal voxel-based morphometry study. J Neurol Neurosurg Psychiatry 81:756–763
Chen JJ, Salat DH, Rosas HD (2012) Complex relationships between cerebral blood flow and brain atrophy in early Huntington’s disease. Neuroimage 59:1043–1051
Hasselbalch SG, Oberg G, Sorensen SA, Andersen AR, Waldemar G, Schmidt JF et al (1992) Reduced regional cerebral blood flow in Huntington’s disease studied by SPECT. J Neurol Neurosurg Psychiatry 55:1018–1023
Zacharoff L, Tkac I, Song Q, Tang C, Bolan PJ, Mangia S et al (2012) Cortical metabolites as biomarkers in the R6/2 model of Huntington’s disease. J Cereb Blood Flow Metab 32:502–514
Jenkins BG, Rosas HD, Chen YC, Makabe T, Myers R, MacDonald M et al (1998) 1H NMR spectroscopy studies of Huntington’s disease: correlations with CAG repeat numbers. Neurology 50:1357–1365
Clarke CE, Lowry M, Quarrell OW (1998) No change in striatal glutamate in Huntington’s disease measured by proton magnetic resonance spectroscopy. Parkinsonism Relat Disord 4:123–127
Sturrock A, Laule C, Decolongon J, Dar Santos R, Coleman AJ, Creighton S et al (2010) Magnetic resonance spectroscopy biomarkers in premanifest and early Huntington disease. Neurology 75:1702–1710
Taylor-Robinson SD, Weeks RA, Bryant DJ, Sargentoni J, Marcus CD, Harding AE et al (1996) Proton magnetic resonance spectroscopy in Huntington’s disease: evidence in favour of the glutamate excitotoxic theory. Mov Disord 11:167–173
Martin WR, Wieler M, Hanstock CC (2007) Is brain lactate increased in Huntington’s disease? J Neurol Sci 263:70–74
Adanyeguh IM, Rinaldi D, Henry PG, Caillet S, Valabregue R, Durr A et al (2015) Triheptanoin improves brain energy metabolism in patients with Huntington disease. Neurology 84:490–495
van den Bogaard SJ, Dumas EM, Teeuwisse WM, Kan HE, Webb A, Roos RA et al (2011) Exploratory 7-Tesla magnetic resonance spectroscopy in Huntington’s disease provides in vivo evidence for impaired energy metabolism. J Neurol 258:2230–2239
Reynolds NC Jr, Prost RW, Mark LP (2005) Heterogeneity in 1H-MRS profiles of presymptomatic and early manifest Huntington’s disease. Brain Res 1031:82–89
Sanchez-Pernaute R, Garcia-Segura JM, del Barrio Alba A, Viano J, de Yebenes JG (1999) Clinical correlation of striatal 1H MRS changes in Huntington’s disease. Neurology 53:806–812
Fu R, Chen CJ, Jinnah HA (2014) Genotypic and phenotypic spectrum in attenuated variants of Lesch–Nyhan disease. Mol Genet Metab 112:280–285
Harris JC, Lee RR, Jinnah HA, Wong DF, Yaster M, Bryan RN (1998) Craniocerebral magnetic resonance imaging measurement and findings in Lesch–Nyhan syndrome. Arch Neurol 55:547–553
Schretlen DJ, Varvaris M, Ho TE, Vannorsdall TD, Gordon B, Harris JC et al (2013) Regional brain volume abnormalities in Lesch–Nyhan disease and its variants: a cross-sectional study. Lancet Neurol 12:1151–1158
Davanzo P, Ke Y, Thomas MA, Anderson C, King B, Belin T et al (1998) Proton MR spectroscopy in Lesch–Nyhan disease. AJNR Am J Neuroradiol 19:672–674
Mead S, Reilly MM (2015) A new prion disease: relationship with central and peripheral amyloidoses. Nat Rev Neurol 11:90–97
Rezaie P, Lantos PL (2001) Microglia and the pathogenesis of spongiform encephalopathies. Brain Res Brain Res Rev 35:55–72
Brown DR (2001) Microglia and prion disease. Microsc Res Tech 54:71–80
Hyare H, Wroe S, Siddique D, Webb T, Fox NC, Stevens J et al (2010) Brain-water diffusion coefficients reflect the severity of inherited prion disease. Neurology 74:658–665
Galanaud D, Haik S, Linguraru MG, Ranjeva JP, Faucheux B, Kaphan E et al (2010) Combined diffusion imaging and MR spectroscopy in the diagnosis of human prion diseases. Am J Neuroradiol 31:1311–1318
Broom KA, Anthony DC, Lowe JP, Griffin JL, Scott H, Blamire AM et al (2007) MRI and MRS alterations in the preclinical phase of murine prion disease: association with neuropathological and behavioural changes. Neurobiol Dis 26:707–717
Sarajlija A, Kisic-Tepavcevic D, Nikolic Z, Savic Pavicevic D, Obradovic S, Djuric M et al (2015) Epidemiology of Rett syndrome in Serbia: prevalence, incidence and survival. Neuroepidemiology 44:1–5
Jellinger K, Armstrong D, Zoghbi HY, Percy AK (1988) Neuropathology of Rett syndrome. Acta Neuropathol 76:142–158
Williams EC, Zhong X, Mohamed A, Li R, Liu Y, Dong Q et al (2014) Mutant astrocytes differentiated from Rett syndrome patients-specific iPSCs have adverse effects on wild-type neurons. Hum Mol Genet 23:2968–2980
Gotoh H, Suzuki I, Maruki K, Mitomo M, Hirasawa K, Sasaki N (2001) Magnetic resonance imaging and clinical findings examined in adulthood-studies on three adults with Rett syndrome. Brain Dev 23(Suppl 1):S118–S121
Khong PL, Lam CW, Ooi CG, Ko CH, Wong VC (2002) Magnetic resonance spectroscopy and analysis of MECP2 in Rett syndrome. Pediatr Neurol 26:205–209
Reiss AL, Faruque F, Naidu S, Abrams M, Beaty T, Bryan RN et al (1993) Neuroanatomy of Rett syndrome: a volumetric imaging study. Ann Neurol 34:227–234
Naidu S, Kaufmann WE, Abrams MT, Pearlson GD, Lanham DC, Fredericksen KA et al (2001) Neuroimaging studies in Rett syndrome. Brain Dev 23(Suppl 1):S62–S71
Ward BC, Kolodny NH, Nag N, Berger-Sweeney JE (2009) Neurochemical changes in a mouse model of Rett syndrome: changes over time and in response to perinatal choline nutritional supplementation. J Neurochem 108:361–371
Horska A, Naidu S, Herskovits EH, Wang PY, Kaufmann WE, Barker PB (2000) Quantitative 1H MR spectroscopic imaging in early Rett syndrome. Neurology 54:715–722
Filosa JA, Morrison HW, Iddings JA, Du W, Kim KJ (2015) Beyond neurovascular coupling, role of astrocytes in the regulation of vascular tone. Neuroscience. doi:10.1016/j.neuroscience.2015.03.064
Fujita T, Katsukawa H, Yodoya E, Wada M, Shimada A, Okada N et al (2005) Transport characteristics of N-acetyl-l-aspartate in rat astrocytes: involvement of sodium-coupled high-affinity carboxylate transporter NaC3/NaDC3-mediated transport system. J Neurochem 93:706–714
Lowe MT, Kim EH, Faull RL, Christie DL, Waldvogel HJ (2013) Dissociated expression of mitochondrial and cytosolic creatine kinases in the human brain: a new perspective on the role of creatine in brain energy metabolism. J Cereb Blood Flow Metab 33:1295–1306
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sherry, E.B., Lee, P. & Choi, IY. In Vivo NMR Studies of the Brain with Hereditary or Acquired Metabolic Disorders. Neurochem Res 40, 2647–2685 (2015). https://doi.org/10.1007/s11064-015-1772-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-015-1772-1