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Cerebral Organic Acid Disorders and Other Disorders of Lysine Catabolism

  • Chapter
Inborn Metabolic Diseases

Zusammenfassung

Thirteen inborn errors of metabolism are described in this chapter. Glutaric aciduria type I, L-2-hydroxyglutaric aciduria, D-2-hydroxyglutaric aciduria (type I and II), D-2-/L-2-hydroxyglutaric aciduria, N-acetylaspartic aciduria, hypoacetylaspartia, and aspartate-glutamate carrier 1 deficiency are all associated with neurological disease of varying severity whereas hyperlysinaemia/saccharopinuria, hydroxylysinuria, 2-amino-/2-oxoadipic aciduria, aminoacylase 1 deficiencyand glutaric aciduria type III are likely non diseases or have an unclear clinical significance, although some patients are retarded and show variable neurological abnormalities.

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References

  1. Hoffmann GF, Gibson KM, Trefz FK et al. (1994) Neurological manifestations of organic acid disorders. Eur J Pediatr 153:S94–100

    Google Scholar 

  2. Dancis J, Hutzler J, Ampola MG et al. (1983) The prognosis of hyperlysinemia: an interim report. Am J Hum Genet 35:438–442

    Google Scholar 

  3. Sacksteder KA, Biery BJ, Morell JC et al. (2000) identification of the α-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia. Am J Hum Genet 66:1736–1743

    Google Scholar 

  4. Przyrembel H (2002) Disorders of ornithine, lysine and tryptophan. In: Blau N, Duran Blaskovics M, Gibson KM (eds) Physician’s guide to the laboratory diagnosis of inherited metabolic disease. Chapman & Hall, London, pp 277–300

    Google Scholar 

  5. Saudubray JM, Rabier D (2007) Biomarkers identified in inborn errors of lysine, arginine and ornithine. J Nutr 137:1669S–1672S

    Google Scholar 

  6. Goodman SI, Browder JA, Hiles RA, Miles BS (1972) Hydroxylysinemia. A disorder due to a defect in the metabolism of free hydroxylysin. Biochem Med 6:344–354

    Google Scholar 

  7. Przyrembel H, Bachmann D, Lombeck I et al. (1975) Alpha-ketoadipic aciduria, a new inborn error of lysine metabolism; biochemical studies. Clin Chim Acta 58:257–269

    Google Scholar 

  8. Xu WY, Gu MM, Sun LH et al. (2012) A nonsense mutation in DHTKD1 causes Charcot-Marie-Tooth disease type 2 in a large Chinese pedigree. Am J Hum Genet 91:1088–1094

    Google Scholar 

  9. Danhauser K, Sauer SW, Haack TB et al. (2012) DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria. Am J Hum Genet 91:1082–1087

    Google Scholar 

  10. Strauss KA, Puffenberger EG, Robinson DL, Morton DH (2003) Type I glutaric aciduria, part 1: natural history of 77 patients. Am J Med Genet 121C:38–52

    Google Scholar 

  11. Kölker 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

    Google Scholar 

  12. 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

    Google Scholar 

  13. Morris AAM, Hoffmann GF, Naughten ER et al. (1999) Glutaric aciduria and suspected child abuse. Arch Dis Childh 80:404–405

    Google Scholar 

  14. Strauss KA, Donelly P, Wintermark M (2010) Cerebral haemodynamics in patients with glutaryl-coenzmye A dehydrogenase deficiency. Brain 133:76–92

    Google Scholar 

  15. Heringer J, Boy SPN, Ensenauer R et al. (2010) Use of guidelines improves the outcome in glutaric aciduria type I. Ann Neurol 68:743–752

    Google Scholar 

  16. 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

    Google Scholar 

  17. 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 280:2180–21836

    Google Scholar 

  18. 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 constitutes a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency. J Neurochem 97:899–910

    Google Scholar 

  19. Goodman SI, Stein DE, Schlesinger S et al. (1998) Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): Review and report of thirty novel mutations. Hum Mutat 12:141–144

    Google Scholar 

  20. Baric I, Wagner L, Feyh P et al. (1999) Sensitivity and specificity of free and total glutaric and 3-hydroxyglutaric acids measurements by stable isotope dilution assays for the diagnosis of glutaric aciduria type I. J Inherit Metab Dis 22:867–882

    Google Scholar 

  21. Lindner M, Kölker S, Schulze A et al. (2004) Neonatal screening for glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis 27:851–859

    Google Scholar 

  22. Christensen E (1993) A fibroblast glutaryl-CoA dehydrogenase assay using detritiation of 3H-labelled glutaryl-CoA: application in the genotyping of the glutaryl-CoA dehydrogenas locus. Clin Chim Acta 220:71–80

    Google Scholar 

  23. Kölker S, Christensen E, Leonard JV et al. (2011) Diagnosis and management of glutaric aciduria type I--revised recommendations. J Inherit Metab Dis 34:677–694

    Google Scholar 

  24. Kölker 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

    Google Scholar 

  25. Strauss KA, Lazovic J, Wintermark M et al. (2007) Multimodal imaging of striatal degeneration in Amish patients with glutaryl-CoA dehydrogenase deficiency. Brain 130:1905–1920

    Google Scholar 

  26. Knerr I, Zschocke J, Trautmann U et al. (2002) Glutaric aciduria type III: a distinctive non-disease. J Inherit Metab Dis 25:483–490

    Google Scholar 

  27. Mailaire S, van Schaftingen E, Veiga-da-Cunha M (2014) C7orf10 encodes succinate-hydroxymethylglutarate CoA-transferase, the enzyme that converts glutarate to glutaryl-CoA. J Inherit Metab Dis 37:13–19

    Google Scholar 

  28. Sherman EA, Strauss KA, Tortorelli S et al. (2008) Genetic mapping of glutaric aciduria, type 3, to chromosome 7 and identification of mutations in C7orf10. Am J Hum Genet 83:604–609

    Google Scholar 

  29. Barth PG, Hoffmann GF, Jaeken J et al. (1993) L-2-Hydroxyglutaric acidemia: clinical and biochemical findings in 12 patients and preliminary report on L-2-hydroxyacid dehydrogenase. J Inherit Metab Dis 16:753–761

    Google Scholar 

  30. Moroni I, D’Incerti L, Farina L et al. (2000) Clinical, biochemical and neuroradiological findings in L-2-hydroxyglutaric aciduria. Neurol Sci 21:103–108

    Google Scholar 

  31. Chen E, Nyhan WL, Jakobs C et al. (1996) L-2-Hydroxyglutaric aciduria: neuropathological correlations and first report of severe neurodegenerative disease and neonatal death. J Inherit Metab Dis 19:335–343

    Google Scholar 

  32. Moroni I, Bugiani L, D’Incerti C et al. (2004) L-2-Hydroxyglutaric aciduria and brain malignant tumors: A predisposing condition? Neurology 62:1882–1884

    Google Scholar 

  33. Rzem R, Veiga-da-Cunha M, Noel G et al. (2004) A gene encoding a putative FAD-dependent L-2-hydroxyglutarate dehydrogenase is mutated in L-2-hydroxyglutaric aciduria. Proc Natl Acad Sci USA 101:16849–16854

    Google Scholar 

  34. Hoffmann GF, Jakobs C, Holmes B et al. (1995) Organic acids in cerebrospinal fluid and plasma of patients with L-2-hydroxyglutaric aciduria. J Inherit Metab Dis 18:189–193

    Google Scholar 

  35. Rzem R, Vincent MF, Schaftingen v E et al. (2007) L-2-Hydroxyglutaric aciduria, a defect of metabolite repair. J Inherit Metab Dis 30:681–689

    Google Scholar 

  36. Topcu M, Jobard F, Halliez S et al. (2004) L-2-Hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localised on chromosome 14q22.1. Hum Mol Genet 13:2803–2811

    Google Scholar 

  37. Gibson KM, Schor DSM, Kok RM et al. (1993) Stable-isotope dilution analysis of D- and L-2-hydroxyglutaric acid: application to the detection and prenatal diagnosis of D- and L-2-hydroxyglutaric acidemias. Pediatr Res 34:277–280

    Google Scholar 

  38. Samuraki M, Komai M, Hasegawa Y et al. (2008) A successfully treated adult patient with L-2-hydroxyglutaric aciduria. Neurology 70:1051–1052

    Google Scholar 

  39. Knaap vd MS, Jakobs C, Hoffmann GF et al. (1999) D-2-Hydroxyglutaric aciduria. Biochemical marker or clinical disease entity? Ann Neurol 45:111–119

    Google Scholar 

  40. Struys EA, Salomons GS, Achouri Y et al. (2005) Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. Am J Hum Genet 76:358–360

    Google Scholar 

  41. Kranendijk M, Struys EA, Schaftingen v E et al. (2010) IDH2 Mutations in patients with D-2-hydroxyglutaric aciduria. Science 330:336

    Google Scholar 

  42. Kranendijk M, Struys EA, Gibson KM et al. (2010) Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria. Hum Mut 31:279–283

    Google Scholar 

  43. Muntau AC, Röschinger W, Merkenschlager A et al. (2000) Combined D-2 and L-2-hydroxyglutaric aciduria with neonatal onset encephalopathy: A third biochemical variant of 2-hydroxyglutaric aciduria? Neuropediatrics 31:137–140

    Google Scholar 

  44. Nota B, Struys EA, Pop A et al. (2013) Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. Am J Human Genet 92:627–631

    Google Scholar 

  45. Mühlhausen C, Salomons GS, Lukacs Z et al. (2014) Combined D2-/L2-hydroxyglutaric aciduria (SLC25A1 deficiency): clinical course and effects of citrate treatment. J Inherit Metab Dis 37:775–781

    Google Scholar 

  46. Matalon R, Michals K, Kaul R (1995) Canavan disease: from spongy degeneration to molecular analysis. J Pediatr 127:511–517

    Google Scholar 

  47. Brismar J, Brismar G, Gascon G, Ozand P (1990) Canavan disease: CT and MR imaging of the brain. Am J Neuroradiol 11:805–810

    Google Scholar 

  48. Madhavarao CN, Arun P, Moffett JR et al. (2005) Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan’s disease. PNAS 102:5221–5226

    Google Scholar 

  49. Baslow MH (2002) Evidence supporting a role for N-acetyl-l-aspartate as a molecular water pump in myelinated neurons in the central nervous system. An analytical review. Neurochem Int 40:295–300

    Google Scholar 

  50. Matalon R, Michals-Matalon K (1998) Molecular basis of Canavan disease. Eur J Paediatr Neurol 2:69–76

    Google Scholar 

  51. Howell VM, Proos AL, LaRue D et al. (2004) Carrier screening for Canavan disease in Australia. J Inherit Metab Dis 27:289–290

    Google Scholar 

  52. Besley GTN, Elpeleg ON, Shaag A et al. (1999) Prenatal diagnosis of Canavan disease: Problems and dilemmas. J Inherit Metab Dis 22:263–266

    Google Scholar 

  53. Assadi M, Janson C, Wan DJ et al. (2010) Lithium citrate reduces excessive intracerebral N-acetylaspartate in Canavan disease. Eur J Paediatr Neurol 14:354–359

    Google Scholar 

  54. Madhavarao CN, Arun P, Anikster Y et al. (2009) Glyceryl triacetate for Canavan disease: A low-dose trial in infants and evaluation of a higher dose for toxicity in the tremor rat model. J Inherit Metab Dis 32:640–650

    Google Scholar 

  55. Leone P, Janson CG, Bilanuk L et al. (2000) Aspartoacylase gene transfer to the mammalian central nervous system with therapeutic implications for Canavan disease. Ann Neurol 48:27–38

    Google Scholar 

  56. McPhee SW, Francis J, Janson CG et al. (2005) Effects of AAV-2-mediated aspartoacylase gene transfer in the tremor rat model of Canavan disease. Brain Res Mol Brain Res 135:112–121

    Google Scholar 

  57. Sass JO, Mohr V, Olbrich H et al. (2006) Mutations of ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism. Am J Hum Genet 78:401–409

    Google Scholar 

  58. Bolthauser E, Schmitt B, Wevers RA et al. (2004) Follow-up of a child with hypoacetylaspartia. Neuropediatrics 35:255–258

    Google Scholar 

  59. Wiame E, Tyteca D, Pierrot N et al. (2010) Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia. Biochem J 425:127–136

    Google Scholar 

  60. Wibom R, Lasorsa FM, Töhönen V et al. (2009) AGC1 deficiency associated with global cerebral hypomyelination. N Engl J Med 361:489–495

    Google Scholar 

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Authors and Affiliations

  1. University Children’s Hospital, Ruprecht-Karls University, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany

    Georg F. Hoffmann & Stefan Kölker

Authors
  1. Georg F. Hoffmann
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  2. Stefan Kölker
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Correspondence to Georg F. Hoffmann or Stefan Kölker .

Editor information

Editors and Affiliations

  1. Department of Neurology, Neurometabolic Unit, Hôpital Pitié Salpêtrière, Paris, France

    Jean-Marie Saudubray

  2. Division of Metabolism, University Children’s Hospital, Zurich, Switzerland

    Matthias R. Baumgartner

  3. Willink Biochemical Genetics Unit Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK

    John Walter

  4. Central Manchester University Hospitals NHS Foundation Trust, St Mary‘s Hospital, Manchester, UK

    John Walter

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Hoffmann, G.F., Kölker, S. (2016). Cerebral Organic Acid Disorders and Other Disorders of Lysine Catabolism. In: Saudubray, JM., Baumgartner, M., Walter, J. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-49771-5_22

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  • DOI: https://doi.org/10.1007/978-3-662-49771-5_22

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-49769-2

  • Online ISBN: 978-3-662-49771-5

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