Journal of Inherited Metabolic Disease

, Volume 30, Issue 5, pp 631–641 | Cite as

Psychiatric manifestations revealing inborn errors of metabolism in adolescents and adults

  • F. Sedel
  • N. Baumann
  • J.-C. Turpin
  • O. Lyon-Caen
  • J.-M. Saudubray
  • D. Cohen
Review

Summary

Inborn errors of metabolism (IEMs) may present in adolescence or adulthood as a psychiatric disorder. In some instances, an IEM is suspected because of informative family history or because psychiatric symptoms form part of a more diffuse clinical picture with systemic, cognitive or motor neurological signs. However, in some cases, psychiatric signs may be apparently isolated. We propose a schematic classification of IEMs into three groups according to the type of psychiatric signs at onset. Group 1 represents emergencies, in which disorders can present with acute and recurrent attacks of confusion, sometimes misdiagnosed as acute psychosis. Diseases in this group include urea cycle defects, homocysteine remethylation defects and porphyrias. Group 2 includes diseases with chronic psychiatric symptoms arising in adolescence or adulthood. Catatonia, visual hallucinations, and aggravation with treatments are often observed. This group includes homocystinurias, Wilson disease, adrenoleukodystrophy and some lysosomal disorders. Group 3 is characterized by mild mental retardation and late-onset behavioural or personality changes. This includes homocystinurias, cerebrotendinous xanthomatosis, nonketotic hyperglycinaemia, monoamine oxidase A deficiency, succinic semialdehyde dehydrogenase deficiency, creatine transporter deficiency, and α and β mannosidosis. Because specific treatments should be more effective at the ‘psychiatric stage’ before the occurrence of irreversible neurological lesions, clinicians should be aware of atypical psychiatric symptoms or subtle organic signs that are suggestive of an IEM. Here we present an overview of IEMs potentially revealed by psychiatric problems in adolescence or adulthood and provide a diagnostic strategy to guide metabolic investigations.

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References

  1. Abbott MH, Folstein SE, Abbey H, Pyeritz RE (1987) Psychiatric manifestations of homocystinuria due to cystathionine beta-synthase deficiency: prevalence, natural history, and relationship to neurologic impairment and vitamin B6-responsiveness. Am J Med Genet 26: 959–969.CrossRefPubMedGoogle Scholar
  2. Akil M, Schwartz JA, Dutchak D, et al (1991) The psychiatric presentations of Wilson’s disease. J Neuropsychiatry Clin Neurosci 3: 377–382.PubMedGoogle Scholar
  3. Angus B, de Silva R, Davidson R, Bone I (1994) A family with adult-onset cerebral adrenoleucodystrophy. J Neurol 241: 497–499.CrossRefPubMedGoogle Scholar
  4. Argov Z, Navon R (1984) Clinical and genetic variations in the syndrome of adult GM2 gangliosidosis resulting from hexosaminidase A deficiency. Ann Neurol 16: 14–20.CrossRefPubMedGoogle Scholar
  5. Arn PH, Hauser ER, Thomas GH et al (1990) Hyperammonemia in women with a mutation at the ornithine carbamoyltransferase locus. A cause of postpartum coma. N Engl J Med 322: 1652–1655.PubMedCrossRefGoogle Scholar
  6. Baumann N, Masson M, Carreau V, Lefevre M, Herschkowitz N, Turpin JC (1991) Adult forms of metachromatic leukodystrophy: clinical and biochemical approach. Dev Neurosci 13: 211–215.CrossRefPubMedGoogle Scholar
  7. Bedilu R, Nummy KA, Cooper A, et al (2002) Variable clinical presentation of lysosomal beta-mannosidosis in patients with null mutations. Mol Genet Metab 77: 282–290.CrossRefPubMedGoogle Scholar
  8. Berger-Plantinga EG, Vanneste JA, Groener JE, van Schooneveld MJ (2004) Adult-onset dementia and retinitis pigmentosa due to mucopolysaccharidosis III-C in two sisters. J Neurol 251: 479–481.CrossRefPubMedGoogle Scholar
  9. Berginer VM, Foster NL, Sadowsky M, et al (1988) Psychiatric disorders in patients with cerebrotendinous xanthomatosis. Am J Psychiatry 145: 354–357.PubMedGoogle Scholar
  10. Blans MJ, Vos PE, Faber HJ, Boers GH (2001) Coma in a young anorexic woman. Lancet 357: 1944.CrossRefPubMedGoogle Scholar
  11. Brunner HG, Nelen MR, van Zandvoort P, et al (1993) X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism. Am J Hum Genet 52: 1032–1039.PubMedGoogle Scholar
  12. Chroni E, Lekka NP, Tsibri E, Economou A, Paschalis C (2001) Acute, progressive akinetic-rigid syndrome induced by neuroleptics in a case of Wilson’s disease. J Neuropsychiatry Clin Neurosci 13: 531–532.PubMedGoogle Scholar
  13. Cohen D, Nicolas JD, Flament MF, et al (2005) Clinical relevance of chronic catatonic schizophrenia in children and adolescents: evidence from a prospective naturalistic study. Schizophr Res 76: 301–308.CrossRefPubMedGoogle Scholar
  14. Crimlisk HL (1997) The little imitator—porphyria: a neuropsychiatric disorder. J Neurol Neurosurg Psychiatry 62: 319–328.CrossRefPubMedGoogle Scholar
  15. Dening TR, Berrios GE (1989) Wilson’s disease. Psychiatric symptoms in 195 cases. Arch Gen Psychiatry 46: 1126–1134.PubMedGoogle Scholar
  16. DiMagno EP, Lowe JE, Snodgrass PJ, Jones JD (1986) Ornithine transcarbamylase deficiency-a cause of bizarre behavior in a man. N Engl J Med 315: 744–747.PubMedCrossRefGoogle Scholar
  17. Dinopoulos A, Kure S, Chuck G, et al (2005) Glycine decarboxylase mutations: a distinctive phenotype of nonketotic hyperglycinemia in adults. Neurology 64: 1255–1257.PubMedGoogle Scholar
  18. Enns GM, O’Brien WE, Kobayashi K, Shinzawa H, Pellegrino JE (2005) Postpartum “psychosis” in mild argininosuccinate synthetase deficiency. Obstet Gynecol 105: 1244–1246.PubMedGoogle Scholar
  19. Estrov Y, Scaglia F, Bodamer OA (2000) Psychiatric symptoms of inherited metabolic disease. J Inherit Metab Dis 23: 2–6.CrossRefPubMedGoogle Scholar
  20. Fattal O, Link J, Quinn K, Cohen BH, Franco K (2007) Psychiatric comorbidity in 36 adults with mitochondrial cytopathies. CNS Spectr 12: 429–438.PubMedGoogle Scholar
  21. Federico A, Palmeri S, Malandrini A, Fabrizi G, Mondelli M, Guazzi GC (1991) The clinical aspects of adult hexosaminidase deficiencies. Dev Neurosci 13: 280–287.CrossRefPubMedGoogle Scholar
  22. Freeman JM, Finkelstein JD, Mudd SH (1975) Folate-responsive homocystinuria and “schizophrenia” A defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity. N Engl J Med 292: 491–496.PubMedCrossRefGoogle Scholar
  23. Gibson KM, Gupta M, Pearl PL, et al (2003) Significant behavioral disturbances in succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria). Biol Psychiatry 54: 763–768.CrossRefPubMedGoogle Scholar
  24. Gravel RA, Kaback MM, Proia RL, Sandhoff K, Suzuki K, Suzuki K (2001) The GM2 gangliosidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc. eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 3827–3865.Google Scholar
  25. Grewal RP (1993) Psychiatric disorders in patients with Fabry’s disease. Int J Psychiatry Med 23: 307–312.CrossRefPubMedGoogle Scholar
  26. Gutschalk A, Harting I, Cantz M, Springer C, Rohrschneider K, Meinck HM (2004) Adult alpha-mannosidosis: clinical progression in the absence of demyelination. Neurology 63: 1744–1746.PubMedGoogle Scholar
  27. Hahn KA, Salomons GS, Tackels-Horne D, et al (2002) X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28. Am J Hum Genet 70: 1349–1356.CrossRefPubMedGoogle Scholar
  28. Hurowitz GI, Silver JM, Brin MF, Williams DT, Johnson WG (1993) Neuropsychiatric aspects of adult-onset Tay–Sachs disease: two case reports with several new findings. J Neuropsychiatry Clin Neurosci 5: 30–36.PubMedGoogle Scholar
  29. Kauppinen R (2005) Porphyrias. Lancet 365: 241–252.PubMedGoogle Scholar
  30. Malm D, Pantel J, Linaker OM (2005) Psychiatric symptoms in alpha-mannosidosis. J Intellect Disabil Res 49: 865–871.CrossRefPubMedGoogle Scholar
  31. Moser HW (1997) Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. Brain 120: 1485–1508.CrossRefPubMedGoogle Scholar
  32. Mudd SH, Skovby F, Levy HL, et al (1985) The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet 37: 1–31.PubMedGoogle Scholar
  33. Navon R (1991) Molecular and clinical heterogeneity of adult GM2 gangliosidosis. Dev Neurosci 13: 295–298.CrossRefPubMedGoogle Scholar
  34. Neudorfer O, Pastores GM, Zeng BJ, Gianutsos J, Zaroff CM, Kolodny EH (2005) Late-onset Tay–Sachs disease: phenotypic characterization and genotypic correlations in 21 affected patients. Genet Med 7: 119–123.CrossRefPubMedGoogle Scholar
  35. Niemann S, Beck M, Seidel G, Spranger J, Vieregge P (1996) Neurology of adult alpha-mannosidosis. J Neurol Neurosurg Psychiatry 61: 116–117.CrossRefPubMedGoogle Scholar
  36. Pasquier F, Lebert F, Petit H, et al (1994) Methylenetetrahydrofolate reductase deficiency revealed by a neuropathy in a psychotic adult. J Neurol Neurosurg Psychiatry 57: 765–766.CrossRefPubMedGoogle Scholar
  37. Rauschka H, Colsch B, Baumann N, et al (2006) Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype. Neurology 67: 859–863.CrossRefPubMedGoogle Scholar
  38. Rosebush PI, Garside S, Levinson AJ, Mazurek MF (1999) The neuropsychiatry of adult-onset adrenoleukodystrophy. J Neuropsychiatry Clin Neurosci 11: 315–327.PubMedGoogle Scholar
  39. Roze E, Gervais D, Demeret S, et al (2003) Neuropsychiatric disturbances in presumed late-onset cobalamin C disease. Arch Neurol 60: 1457–1462.CrossRefPubMedGoogle Scholar
  40. Ryan MM, Sidhu RK, Alexander J, Megerian JT (2002) Homocystinuria presenting as psychosis in an adolescent. J Child Neurol 17: 859–860.CrossRefPubMedGoogle Scholar
  41. Saudubray JM, Desguerre I, Sedel F, Charpentier C (2006) A clinical approach to inherited metabolic disorders. In: Saudubray JM, van den Berghe G, Walter J, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. Berlin: Springer-Verlag, 3–48.CrossRefGoogle Scholar
  42. Sedel F, Friderici K, Nummy K, et al (2006) Atypical Gilles de la Tourette syndrome with beta-mannosidase deficiency. Arch Neurol 63: 129–131.CrossRefPubMedGoogle Scholar
  43. Sedel F, Lyon-Caen O, Saudubray JM (2007) Inborn errors of metabolism in adult neurology—a clinical approach focused on treatable diseases. Nat Clin Pract Neurol 3: 279–290.CrossRefPubMedGoogle Scholar
  44. Sereni C, Ruel M, Iba-Zizen T, Baumann N, Marteau R, Paturneau-Jouas M (1987) Adult adrenoleukodystrophy: a sporadic case? J Neurol Sci 80: 121–128.CrossRefPubMedGoogle Scholar
  45. Sevin M, Lesca G, Baumann N, et al (2007) The adult form of Niemann–Pick disease type C. Brain 130: 120–133.CrossRefPubMedGoogle Scholar
  46. Turpin JC, Baumann N (2003) Presenting psychiatric and cognitive disorders in adult neurolipidoses. Rev Neurol (Paris) 159: 637–647.Google Scholar
  47. Van Diggelen OP, Thobois S, Tilikete C, et al (2001) Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: first adult-onset patients of a childhood disease. Ann Neurol 50: 269–272.CrossRefPubMedGoogle Scholar
  48. Van Geel BM, Bezman L, Loes DJ, Moser HW, Raymond GV (2001) Evolution of phenotypes in adult male patients with X-linked adrenoleukodystrophy. Ann Neurol 49: 186–194.CrossRefPubMedGoogle Scholar
  49. Walshe JM, Yealland M (1992) Wilson’s disease: the problem of delayed diagnosis. J Neurol Neurosurg Psychiatry 55: 692–696.CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM and Springer 2007

Authors and Affiliations

  • F. Sedel
    • 1
    • 2
  • N. Baumann
    • 3
  • J.-C. Turpin
    • 3
  • O. Lyon-Caen
    • 1
  • J.-M. Saudubray
    • 5
  • D. Cohen
    • 4
  1. 1.Federation of Nervous System DiseasesHôpital de la SalpêtrièreParis cedex 13France
  2. 2.National Reference Center for Lysosomal DiseasesHôpital de la SalpêtrièreParisFrance
  3. 3.Unité mixte de recherche INSERM U-711Hôpital de la SalpêtrièreParisFrance
  4. 4.Service de Psychiatrie de l’Enfant et de l’AdolescentHôpital de la Salpêtrière and Université Pierre et Marie Curie (Paris VI)ParisFrance
  5. 5.National Reference Center for Metabolic DiseasesNecker-enfants malades Hospital and Université René Descartes (Paris V), Assistance Publique-Hôpitaux de ParisParisFrance

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