Abstract
Organic acidurias (synonym, organic acid disorders, OADs) are a heterogenous group of inherited metabolic diseases delineated with the implementation of gas chromatography/mass spectrometry in metabolic laboratories starting in the 1960s and 1970s. Biochemically, OADs are characterized by accumulation of mono-, di- and/or tricarboxylic acids (“organic acids”) and corresponding coenzyme A, carnitine and/or glycine esters, some of which are considered toxic at high concentrations. Clinically, disease onset is variable, however, affected individuals may already present during the newborn period with life-threatening acute metabolic crises and acute multi-organ failure. Tandem mass spectrometry-based newborn screening programmes, in particular for isovaleric aciduria and glutaric aciduria type 1, have significantly reduced diagnostic delay. Dietary treatment with low protein intake or reduced intake of the precursor amino acid(s), carnitine supplementation, cofactor treatment (in responsive patients) and nonadsorbable antibiotics is commonly used for maintenance treatment. Emergency treatment options with high carbohydrate/glucose intake, pharmacological and extracorporeal detoxification of accumulating toxic metabolites for intensified therapy during threatening episodes exist. Diagnostic and therapeutic measures have improved survival and overall outcome in individuals with OADs. However, it has become increasingly evident that the manifestation of late disease complications cannot be reliably predicted and prevented. Conventional metabolic treatment often fails to prevent irreversible organ dysfunction with increasing age, even if patients are considered to be “metabolically stable”. This has challenged our understanding of OADs and has elicited the discussion on optimized therapy, including (early) organ transplantation, and long-term care.
Similar content being viewed by others
Abbreviations
- CNS:
-
Central nervous system
- CRF:
-
Chronic renal failure
- EO:
-
Early (i.e. neonatal) disease onset
- GA1:
-
Glutaric aciduria type 1
- IVA:
-
Isovaleric aciduria
- LO:
-
Late disease onset (i.e. after the newborn period)
- MRI:
-
Magnetic resonance imaging
- MMA:
-
Isolated methylmalonic aciduria
- OAD(s):
-
Organic aciduria(s)
- PA:
-
Propionic aciduria
- QTc :
-
Corrected QT interval
References
Arias C, Raimann E, Peredo P et al (2014) Propionic acidemia and optic neuropathy: a report of two cases. JIMD Rep 12:1–4
Arrizza C, De Gottardi A, Foglia E, Baumgartner M, Gautschi M, Nuoffer JM (2015) Reversal of cardiomyopathy in propionic acidemia after liver transplantation: a 10-year follow-up. Transpl Int 28:1447–1450
Azar MR, Shakiba M, Tafreshi RI, Rashed MS (2007) Heart failure in a patient with methylmalonic acidemia. Mol Genet Metab 92:188
Bahr O, Mader I, Zschocke J, Dichgans J, Schulz JB (2002) Adult onset glutaric aciduria type I presenting with a leukoencephalopathy. Neurology 59:1802–1804
Baker EH, Sloan JL, Hauser NS et al (2015) MRI characteristics of globus pallidus infarcts in isolated methylmalonic acidemia. AJNR Am J Neuroradiol 36:194–201
Baric I, Wagner L, Feyh P, Liesert M, Buckel W, Hoffmann GF (1999) Sensitivity and specificity of free and total glutaric acid and 3-hydroxyglutaric acid measurements by stable-isotope dilution assays for the diagnosis of glutaric aciduria type I. J Inherit Metab Dis 22:867–881
Barshes NR, Vanatta JM, Patel AJ et al (2006) Evaluation and management of patients with propionic acidemia undergoing liver transplantation: a comprehensive review. Pediatr Transplant 10:773–781
Baumgartner D, Scholl-Burgi S, Sass JO et al (2007) Prolonged QTc intervals and decreased left ventricular contractility in patients with propionic acidemia. J Pediatr 150:192–197
Baumgartner MR, Horster F, Dionisi-Vici C et al (2014) Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis 9:130
Biagosch C, Ediga RD, Hensler SV et al (2017) Elevated glutaric acid levels in Dhtkd1−/Gcdh- double knockout mice challenge our current understanding of lysine metabolism. Biochim Biophys Acta 1863:2220–2228
Boy N, Heringer J, Haege G et al (2015) A cross-sectional controlled developmental study of neuropsychological functions in patients with glutaric aciduria type I. Orphanet J Rare Dis 10:163
Boy N, Heringer J, Brackmann R et al (2017a) Extrastriatal changes in patients with late-onset glutaric aciduria type I highlight the risk of long-term neurotoxicity. Orphanet J Rare Dis 12:77
Boy N, Muhlhausen C, Maier EM et al (2017b) Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision. J Inherit Metab Dis 40:75–101
Brassier A, Boyer O, Valayannopoulos V et al (2013) Renal transplantation in 4 patients with methylmalonic aciduria: a cell therapy for metabolic disease. Mol Genet Metab 110:106–110
Brismar J, Ozand PT (1995) CT and MR of the brain in glutaric acidemia type I: a review of 59 published cases and a report of 5 new patients. AJNR Am J Neuroradiol 16:675–683
Castelnovi C, Moseley K, Yano S (2010) Maternal isovaleric acidemia: observation of distinctive changes in plasma amino acids and carnitine profiles during pregnancy. Clin Chim Acta 411:2101–2103
Chapman KA, Summar ML, Enns GM (2012) Propionic acidemia: to liver transplant or not to liver transplant? Pediatr Transplant 16:209–210
Charbit-Henrion F, Lacaille F, McKiernan P et al (2015) Early and late complications after liver transplantation for propionic acidemia in children: a two centers study. Am J Transplant 15:786–791
Christensen E, Ribes A, Merinero B, Zschocke J (2004) Correlation of genotype and phenotype in glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis 27:861–868
Couce ML, Lopez-Suarez O, Boveda MD et al (2013) Glutaric aciduria type I: outcome of patients with early- versus late-diagnosis. Eur J Paediatr Neurol 17:383–389
Coude FX, Sweetman L, Nyhan WL (1979) Inhibition by propionyl-coenzyme a of N-acetylglutamate synthetase in rat liver mitochondria. A possible explanation for hyperammonemia in propionic and methylmalonic acidemia. J Clin Invest 64:1544–1551
Coude FX, Ogier H, Grimber G et al (1982) Correlation between blood ammonia concentration and organic acid accumulation in isovaleric and propionic acidemia. Pediatrics 69:115–117
Crombez EA, Cederbaum SD, Spector E et al (2008) Maternal glutaric acidemia, type I identified by newborn screening. Mol Genet Metab 94:132–134
de Rivero Vaccari JP, Patel HH, Brand FJ III, Perez-Pinzon MA, Bramlett HM, Raval AP (2016) Estrogen receptor beta signaling alters cellular inflammasomes activity after global cerebral ischemia in reproductively senescence female rats. J Neurochem 136:492–496
Deodato F, Boenzi S, Santorelli FM, Dionisi-Vici C (2006) Methylmalonic and propionic aciduria. Am J Med Genet C Semin Med Genet 142C:104–112
Dionisi-Vici C, Deodato F, Roschinger W, Rhead W, Wilcken B (2006) ‘Classical’ organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry. J Inherit Metab Dis 29:383–389
du Moulin M, Thies B, Blohm M, et al (2017) Glutaric aciduria type 1 and acute renal failure: case report and suggested pathomechanisms. JIMD Rep. https://doi.org/10.1007/8904_2017_44
Ensenauer R, Vockley J, Willard JM et al (2004) A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening. Am J Hum Genet 75:1136–1142
Fagiuoli S, Daina E, D’Antiga L, Colledan M, Remuzzi G (2013) Monogenic diseases that can be cured by liver transplantation. J Hepatol 59:595–612
Feinstein JA, O’Brien K (2003) Acute metabolic decompensation in an adult patient with isovaleric acidemia. South Med J 96:500–503
Fenton WA, Gravel RA, Rosenblatt DS (2001) Disorders of propionate and methylmalonate metabolism. In: Scriver CR, Beaudet AL, Sly WS et al (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York
Fowler B, Leonard JV, Baumgartner MR (2008) Causes of and diagnostic approach to methylmalonic acidurias. J Inherit Metab Dis 31:350–360
Fragaki K, Cano A, Benoist JF et al (2011) Fatal heart failure associated with CoQ10 and multiple OXPHOS deficiency in a child with propionic acidemia. Mitochondrion 11:533–536
Fraidakis MJ, Liadinioti C, Stefanis L et al (2015) Rare late-onset presentation of glutaric aciduria type I in a 16-year-old woman with a novel GCDH mutation. JIMD Rep 18:85–92
Fraser JL, Venditti CP (2016) Methylmalonic and propionic acidemias: clinical management update. Curr Opin Pediatr 28:682–693
Garcia P, Martins E, Diogo L et al (2008) Outcome of three cases of untreated maternal glutaric aciduria type I. Eur J Pediatr 167:569–573
Gitiaux C, Roze E, Kinugawa K et al (2008) Spectrum of movement disorders associated with glutaric aciduria type 1: a study of 16 patients. Mov Disord 23:2392–2397
Grunert SC, Wendel U, Lindner M et al (2012) Clinical and neurocognitive outcome in symptomatic isovaleric acidemia. Orphanet J Rare Dis 7:9
Grunert SC, Bodi I, Odening KE (2017) Possible mechanisms for sensorineural hearing loss and deafness in patients with propionic acidemia. Orphanet J Rare Dis 12:30
Haarmann A, Mayr M, Kolker S et al (2013) Renal involvement in a patient with cobalamin a type (cblA) methylmalonic aciduria: a 42-year follow-up. Mol Genet Metab 110:472–476
Habets DD, Schaper NC, Rogozinski H et al (2012) Biochemical monitoring and management during pregnancy in patients with isovaleric acidaemia is helpful to prevent metabolic decompensation. JIMD Rep 3:83–89
Harting I, Neumaier-Probst E, Seitz A et al (2009) Dynamic changes of striatal and extrastriatal abnormalities in glutaric aciduria type I. Brain 132:1764–1782
Harting I, Boy N, Heringer J et al (2015) (1)H-MRS in glutaric aciduria type 1: impact of biochemical phenotype and age on the cerebral accumulation of neurotoxic metabolites. J Inherit Metab Dis 38:829–838
Heringer J, Boy SP, Ensenauer R et al (2010) Use of guidelines improves the neurological outcome in glutaric aciduria type I. Ann Neurol 68:743–752
Heringer J, Valayannopoulos V, Lund AM et al (2016) Impact of age at onset and newborn screening on outcome in organic acidurias. J Inherit Metab Dis 39:341–353
Herskovitz M, Goldsher D, Sela BA, Mandel H (2013) Subependymal mass lesions and peripheral polyneuropathy in adult-onset glutaric aciduria type I. Neurology 81:849–850
Horster F, Baumgartner MR, Viardot C et al (2007) Long-term outcome in methylmalonic acidurias is influenced by the underlying defect (mut0, mut-, cblA, cblB). Pediatr Res 62:225–230
Horster F, Garbade SF, Zwickler T et al (2009) Prediction of outcome in isolated methylmalonic acidurias: combined use of clinical and biochemical parameters. J Inherit Metab Dis 32:630–639
Horster F, Kolker S, Loeber JG, Cornel MC, Hoffmann GF, Burgard P (2017) Newborn screening programmes in Europe, arguments and efforts regarding harmonisation: focus on organic Acidurias. JIMD Rep 32:105–115
Ianchulev T, Kolin T, Moseley K, Sadun A (2003) Optic nerve atrophy in propionic acidemia. Ophthalmology 110:1850–1854
Jacquemyn Y, Den Hartog M, Eyskens F (2014) Methylmalonic acidaemia in pregnancy. BMJ Case Rep. https://doi.org/10.1136/bcr-2014-203723
Jameson E, Walter J (2008) Cardiac arrest secondary to long QT(C )in a child with propionic acidemia. Pediatr Cardiol 29:969–970
Kahler SG, Sherwood WG, Woolf D et al (1994) Pancreatitis in patients with organic acidemias. J Pediatr 124:239–243
Kakavand B, Schroeder VA, Di Sessa TG (2006) Coincidence of long QT syndrome and propionic acidemia. Pediatr Cardiol 27:160–161
Kasahara M, Sakamoto S, Kanazawa H et al (2012) Living-donor liver transplantation for propionic acidemia. Pediatr Transplant 16:230–234
Kimmoun A, Abboud G, Strazeck J, Merten M, Gueant JL, Feillet F (2008) Acute decompensation of isovaleric acidemia induced by Graves’ disease. Intensive Care Med 34:2315–2316
Kolker S, Pawlak V, Ahlemeyer B et al (2002) NMDA receptor activation and respiratory chain complex V inhibition contribute to neurodegeneration in d-2-hydroxyglutaric aciduria. Eur J Neurosci 16:21–28
Kolker S, Garbade SF, Greenberg CR et al (2006) Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency. Pediatr Res 59:840–847
Kolker S, Garbade SF, Boy N et al (2007) Decline of acute encephalopathic crises in children with glutaryl-CoA dehydrogenase deficiency identified by newborn screening in Germany. Pediatr Res 62:357–363
Kolker S, Garcia-Cazorla A, Valayannopoulos V et al (2015a) The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation. J Inherit Metab Dis 38:1041–1057
Kolker S, Valayannopoulos V, Burlina AB et al (2015b) The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype. J Inherit Metab Dis 38:1059–1074
Korman SH, Jakobs C, Darmin PS et al (2007) Glutaric aciduria type 1: clinical, biochemical and molecular findings in patients from Israel. Eur J Paediatr Neurol 11:81–89
Kulkens S, Harting I, Sauer S et al (2005) Late-onset neurologic disease in glutaryl-CoA dehydrogenase deficiency. Neurology 64:2142–2144
Lam C, Desviat LR, Perez-Cerda C, Ugarte M, Barshop BA, Cederbaum S (2011) 45-year-old female with propionic acidemia, renal failure, and premature ovarian failure; late complications of propionic acidemia? Mol Genet Metab 103:338–340
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
Langendonk JG, Roos JC, Angus L et al (2012) A series of pregnancies in women with inherited metabolic disease. J Inherit Metab Dis 35:419–424
Lee CS, Chien YH, Peng SF et al (2013) Promising outcomes in glutaric aciduria type I patients detected by newborn screening. Metab Brain Dis 28:61–67
Leonard JV, Walter JH, McKiernan PJ (2001) The management of organic acidaemias: the role of transplantation. J Inherit Metab Dis 24:309–311
Lewey J, Haythe J (2014) Cardiomyopathy in pregnancy. Semin Perinatol 38:309–317
Loeber JG, Burgard P, Cornel MC et al (2012) Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 1. From blood spot to screening result. J Inherit Metab Dis 35:603–611
Mardach R, Verity MA, Cederbaum SD (2005) Clinical, pathological, and biochemical studies in a patient with propionic acidemia and fatal cardiomyopathy. Mol Genet Metab 85:286–290
Marquard J, El Scheich T, Klee D et al (2011) Chronic pancreatitis in branched-chain organic acidurias--a case of methylmalonic aciduria and an overview of the literature. Eur J Pediatr 170:241–245
Martinez Alvarez L, Jameson E, Parry NR, Lloyd C, Ashworth JL (2016) Optic neuropathy in methylmalonic acidemia and propionic acidemia. Br J Ophthalmol 100:98–104
Martin-Hernandez E, Lee PJ, Micciche A, Grunewald S, Lachmann RH (2009) Long-term needs of adult patients with organic acidaemias: outcome and prognostic factors. J Inherit Metab Dis 32:523–533
McClelland VM, Bakalinova DB, Hendriksz C, Singh RP (2009) Glutaric aciduria type 1 presenting with epilepsy. Dev Med Child Neurol 51:235–239
Melo DR, Kowaltowski AJ, Wajner M, Castilho RF (2011) Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic acidemia. J Bioenerg Biomembr 43:39–46
Moammar H, Cheriyan G, Mathew R, Al-Sannaa N (2010) Incidence and patterns of inborn errors of metabolism in the Eastern Province of Saudi Arabia, 1983-2008. Ann Saudi Med 30:271–277
Moorthie S, Cameron L, Sagoo GS, Bonham JR, Burton H (2014) Systematic review and meta-analysis to estimate the birth prevalence of five inherited metabolic diseases. J Inherit Metab Dis 37:889–898
Morath MA, Okun JG, Muller IB et al (2008) Neurodegeneration and chronic renal failure in methylmalonic aciduria--a pathophysiological approach. J Inherit Metab Dis 31:35–43
Morath MA, Horster F, Sauer SW (2013) Renal dysfunction in methylmalonic acidurias: review for the pediatric nephrologist. Pediatr Nephrol 28:227–235
Morris AA, Hoffmann GF, Naughten ER, Monavari AA, Collins JE, Leonard JV (1999) Glutaric aciduria and suspected child abuse. Arch Dis Child 80:404–405
Muhlhausen C, Ott N, Chalajour F et al (2006) Endothelial effects of 3-hydroxyglutaric acid: implications for glutaric aciduria type I. Pediatr Res 59:196–202
Mutze U, Roth A, Weigel JF et al (2011) Transition of young adults with phenylketonuria from pediatric to adult care. J Inherit Metab Dis 34:701–709
Mutze U, Thiele AG, Baerwald C, Ceglarek U, Kiess W, Beblo S (2016) Ten years of specialized adult care for phenylketonuria - a single-centre experience. Orphanet J Rare Dis 11:27
Nagao M, Tanaka T, Morii M, Wakai S, Horikawa R, Kasahara M (2013) Improved neurologic prognosis for a patient with propionic acidemia who received early living donor liver transplantation. Mol Genet Metab 108:25–29
Naughten ER, Mayne PD, Monavari AA, Goodman SI, Sulaiman G, Croke DT (2004) Glutaric aciduria type I: outcome in the Republic of Ireland. J Inherit Metab Dis 27:917–920
Niemi AK, Kim IK, Krueger CE et al (2015) Treatment of methylmalonic acidemia by liver or combined liver-kidney transplantation. J Pediatr 166(1455–1461):e1451
Nizon M, Ottolenghi C, Valayannopoulos V et al (2013) Long-term neurological outcome of a cohort of 80 patients with classical organic acidurias. Orphanet J Rare Dis 8:148
Okun JG, Horster F, Farkas LM et al (2002) Neurodegeneration in methylmalonic aciduria involves inhibition of complex II and the tricarboxylic acid cycle, and synergistically acting excitotoxicity. J Biol Chem 277:14674–14680
Pena L, Franks J, Chapman KA et al (2012) Natural history of propionic acidemia. Mol Genet Metab 105:5–9
Pierson TM, Nezhad M, Tremblay MA et al (2015) Adult-onset glutaric aciduria type I presenting with white matter abnormalities and subependymal nodules. Neurogenetics 16:325–328
Pinar-Sueiro S, Martinez-Fernandez R, Lage-Medina S, Aldamiz-Echevarria L, Vecino E (2010) Optic neuropathy in methylmalonic acidemia: the role of neuroprotection. J Inherit Metab Dis 33(Suppl 3):S199–S203
Pinto A, Daly A, Evans S et al (2017) Dietary practices in isovaleric acidemia: a European survey. Mol Genet Metab Rep 12:16–22
Pitchumoni CS, Arguello P, Agarwal N, Yoo J (1996) Acute pancreatitis in chronic renal failure. Am J Gastroenterol 91:2477–2482
Pode-Shakked B, Marek-Yagel D, Rubinshtein M et al (2014) Glutaric Aciduria type I and acute renal failure - coincidence or causality? Mol Genet Metab Rep 1:170–175
Poge AP, Autschbach F, Korall H, Trefz FK, Mayatepek E (1997) Early clinical manifestation of glutaric aciduria type I and nephrotic syndrome during the first months of life. Acta Paediatr 86:1144–1147
Prada CE, Al Jasmi F, Kirk EP et al (2011) Cardiac disease in methylmalonic acidemia. J Pediatr 159:862–864
Radmanesh A, Zaman T, Ghanaati H, Molaei S, Robertson RL, Zamani AA (2008) Methylmalonic acidemia: brain imaging findings in 52 children and a review of the literature. Pediatr Radiol 38:1054–1061
Raval DB, Merideth M, Sloan JL et al (2015) Methylmalonic acidemia (MMA) in pregnancy: a case series and literature review. J Inherit Metab Dis 38:839–846
Ravn K, Chloupkova M, Christensen E et al (2000) High incidence of propionic acidemia in greenland is due to a prevalent mutation, 1540insCCC, in the gene for the beta-subunit of propionyl CoA carboxylase. Am J Hum Genet 67:203–206
Rela M, Battula N, Madanur M et al (2007) Auxiliary liver transplantation for propionic acidemia: a 10-year follow-up. Am J Transplant 7:2200–2203
Rodriguez-Gonzalez M, Castellano-Martinez A (2016) Long QTc syndrome and Propionic Acidemia. Indian Pediatr 53:841
Romano S, Valayannopoulos V, Touati G et al (2010) Cardiomyopathies in propionic aciduria are reversible after liver transplantation. J Pediatr 156:128–134
Ruppert T, Schumann A, Grone HJ et al (2015) Molecular and biochemical alterations in tubular epithelial cells of patients with isolated methylmalonic aciduria. Hum Mol Genet 24:7049–7059
Sauer SW, Okun JG, Schwab MA et al (2005) Bioenergetics in glutaryl-coenzyme a dehydrogenase deficiency: a role for glutaryl-coenzyme a. J Biol Chem 280:21830–21836
Sauer SW, Okun JG, Fricker G et al (2006) Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency. J Neurochem 97:899–910
Sauer SW, Okun JG, Hoffmann GF, Koelker S, Morath MA (2008) Impact of short- and medium-chain organic acids, acylcarnitines, and acyl-CoAs on mitochondrial energy metabolism. Biochim Biophys Acta 1777:1276–1282
Schlenzig JS, Poggi-Travert F, Laurent J et al (1995) Liver transplantation in two cases of propionic acidaemia. J Inherit Metab Dis 18:448–461
Schmitt CP, Mehls O, Trefz FK, Horster F, Weber TL, Kolker S (2004) Reversible end-stage renal disease in an adolescent patient with methylmalonic aciduria. Pediatr Nephrol 19:1182–1184
Schwab MA, Sauer SW, Okun JG et al (2006) Secondary mitochondrial dysfunction in propionic aciduria: a pathogenic role for endogenous mitochondrial toxins. Biochem J 398:107–112
Scott Schwoerer J, van Calcar S, Rice GM, Deline J (2016) Successful pregnancy and delivery in a woman with propionic acidemia from the Amish community. Mol Genet Metab Rep 8:4–7
Shchelochkov OA, Dickinson K, Scharschmidt BF, Lee B, Marino M, Le Mons C (2016) Barriers to drug adherence in the treatment of urea cycle disorders: assessment of patient, caregiver and provider perspectives. Mol Genet Metab Rep 8:43–47
Sloan JL, Manoli I, Venditti CP (2015) Liver or combined liver-kidney transplantation for patients with isolated methylmalonic acidemia: who and when? J Pediatr 166:1346–1350
Spinty S, Rogozinski H, Lealman GT, Wraith JE (2002) Second case of a successful pregnancy in maternal isovaleric acidaemia. J Inherit Metab Dis 25:697–698
Stellmer F, Keyser B, Burckhardt BC et al (2007) 3-Hydroxyglutaric acid is transported via the sodium-dependent dicarboxylate transporter NaDC3. J Mol Med (Berl) 85:763–770
Strauss KA, Puffenberger EG, Robinson DL, Morton DH (2003) Type I glutaric aciduria, part 1: natural history of 77 patients. Am J Med Genet C Semin Med Genet 121C:38–52
Strauss KA, Donnelly P, Wintermark M (2010) Cerebral haemodynamics in patients with glutaryl-coenzyme a dehydrogenase deficiency. Brain 133:76–92
Strauss KA, Brumbaugh J, Duffy A et al (2011) Safety, efficacy and physiological actions of a lysine-free, arginine-rich formula to treat glutaryl-CoA dehydrogenase deficiency: focus on cerebral amino acid influx. Mol Genet Metab 104:93–106
Tanaka K, Budd MA, Efron ML, Isselbacher KJ (1966) Isovaleric acidemia: a new genetic defect of leucine metabolism. Proc Natl Acad Sci U S A 56:236–242
Thies B, Meyer-Schwesinger C, Lamp J et al (2013) Acute renal proximal tubule alterations during induced metabolic crises in a mouse model of glutaric aciduria type 1. Biochim Biophys Acta 1832:1463–1472
Traber G, Baumgartner MR, Schwarz U, Pangalu A, Donath MY, Landau K (2011) Subacute bilateral visual loss in methylmalonic acidemia. J Neuroophthalmol 31:344–346
Tuncel AT, Ruppert T, Wang BT et al (2015) Maleic acid--but not structurally related Methylmalonic acid--interrupts energy metabolism by impaired calcium homeostasis. PLoS One 10:e0128770
Ugarte M, Perez-Cerda C, Rodriguez-Pombo P et al (1999) Overview of mutations in the PCCA and PCCB genes causing propionic acidemia. Hum Mutat 14:275–282
Van Calcar SC (2015) Nutrition management during pregnancy: maple syrup urine disease, propionic acidemia, methylmalonic acidemia and urea cycle disorders. In: Bernstein L, Rohr F, Helm J (eds) Nutrition management of inherited metabolic diseases. Springer, Cham, p 229–240
Van Calcar SC, Harding CO, Davidson SR, Barness LA, Wolff JA (1992) Case reports of successful pregnancy in women with maple syrup urine disease and propionic acidemia. Am J Med Genet 44:641–646
Vara R, Turner C, Mundy H et al (2011) Liver transplantation for propionic acidemia in children. Liver Transpl 17:661–667
Vernon HJ, Bagnasco S, Hamosh A, Sperati CJ (2014) Chronic kidney disease in an adult with propionic acidemia. JIMD Rep 12:5–10
Vester ME, Bilo RA, Karst WA, Daams JG, Duijst WL, van Rijn RR (2015) Subdural hematomas: glutaric aciduria type 1 or abusive head trauma? A systematic review. Forensic Sci Med Pathol 11:405–415
Vester ME, Visser G, Wijburg FA, van Spronsen FJ, Williams M, van Rijn RR (2016) Occurrence of subdural hematomas in Dutch glutaric aciduria type 1 patients. Eur J Pediatr 175:1001–1006
Viau K, Ernst SL, Vanzo RJ, Botto LD, Pasquali M, Longo N (2012) Glutaric acidemia type 1: outcomes before and after expanded newborn screening. Mol Genet Metab 106:430–438
Vilarinho L, Rocha H, Sousa C et al (2010) Four years of expanded newborn screening in Portugal with tandem mass spectrometry. J Inherit Metab Dis 33(Suppl 3):S133–S138
Vockley J, Ensenauer R (2006) Isovaleric acidemia: new aspects of genetic and phenotypic heterogeneity. Am J Med Genet C Semin Med Genet 142C:95–103
Williams ZR, Hurley PE, Altiparmak UE et al (2009) Late onset optic neuropathy in methylmalonic and propionic acidemia. Am J Ophthalmol 147:929–933
Witters P, Debbold E, Crivelly K et al (2016) Autism in patients with propionic acidemia. Mol Genet Metab 119:317–321
Zielonka M, Braun K, Bengel A, Seitz A, Kolker S, Boy N (2015) Severe acute subdural hemorrhage in a patient with glutaric aciduria type I after minor head trauma: a case report. J Child Neurol 30:1065–1069
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
A. T. Tuncel, N. Boy, M. A. Morath, F. Hörster, and U. Mütze declare that they have no conflict of interest.
Stefan Kölker has received speaker honorarium from Vitaflo, Nutricia (Danone group) and Orphan Europe (Recordati group) and has received project grants from Horizon Pharma International Limited and Orphan Europe SARL (Recordati group).
Informed consent
Not applicable.
Animal rights
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
Communicated by: Manuel Schiff
Rights and permissions
About this article
Cite this article
Tuncel, A.T., Boy, N., Morath, M.A. et al. Organic acidurias in adults: late complications and management. J Inherit Metab Dis 41, 765–776 (2018). https://doi.org/10.1007/s10545-017-0135-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10545-017-0135-2