Psychiatric manifestations revealing inborn errors of metabolism in adolescents and adults

Abstract

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 alpha and beta 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.

Autism Spectrum Disorder in a Child with Propionic Acidemia

“…Alternatively, it is possible that the patient was already vulnerable to autism due to some other reason and that PA acted only as a trigger, a view consistent with the so-called two-hit hypothesis of the disorder (Ghaziuddin 2000). Noteworthy, urea cycle disorders, characterized by hyperammonemia, may present with confusion, bizarre behavior, and autisticlike symptoms (Gorker and Tuzun 2005;Sedel et al 2007). It is possible that the recurrent bouts of hyperammonemia played a role in the development of the autistic symptoms in our patient.…”

Aetiology Based Diagnosis and Treatment Selection in Intellectually Disabled People with Challenging Behaviours

“…In case of lysosomal disease such as Niemann-Pick type C (mutation NPC1 gene; 18q11.2 [OMIM:257220] or NPC2 gene; 14q24.3 [OMIM:607625]) a late onset presentation may, apart from pre-existing (mild) developmental delay, manifest firstly with a schizophrenia-like psychosis with or without catatonic symptoms [83,84]. Another example is mucopolysaccharidosis type IIIB (MPSIIIB; Sanfilippo B; OMIM: 252920) that is caused by a mutation in the NAGLU gene (17q21.1; OMIM: 609701) resulting in a deficiency of N-acetyl--D-glucosaminidase.…”

Variants of urea cycle disorders

“…Leider werden oft zunächst andere Erklärungen vermutet und behandelt [15,21,23], im vorliegenden Beispiel durch die Therapie mit Valproat [11]. Valproinsäu- …”