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Diagnostic and Treatment Implications of Psychosis Secondary to Treatable Metabolic Disorders in Adults: A Systematic Review


Diagnostic and Treatment Implications of Psychosis Secondary to Treatable Metabolic Disorders in Adults: A Systematic Review

Olivier Bonnot et al. Orphanet J Rare Dis.


Objective: It is important for psychiatrists to be aware of certain inborn errors of metabolism (IEMs) as these rare disorders can present as psychosis, and because definitive treatments may be available for treating the underlying metabolic cause. A systematic review was conducted to examine IEMs that often present with schizophrenia-like symptoms.

Data sources: Published literature on MEDLINE was assessed regarding diseases of homocysteine metabolism (DHM; cystathionine beta-synthase deficiency [CbS-D] and homocysteinemia due to methyltetrahydrofolate reductase deficiency [MTHFR-D]), urea cycle disorders (UCD), acute porphyria (POR), Wilson disease (WD), cerebrotendinous-xanthomatosis (CTX) and Niemann-Pick disease type C (NP-C).

Study selection: Case reports, case series or reviews with original data regarding psychiatric manifestations and cognitive impairment published between January 1967 and June 2012 were included based on a standardized four-step selection process.

Data extraction: All selected articles were evaluated for descriptions of psychiatric signs (type, severity, natural history and treatment) in addition to key disease features.

Results: A total of 611 records were identified. Information from CbS-D (n = 2), MTHFR-D (n = 3), UCD (n = 8), POR (n = 12), WD (n = 11), CTX (n = 14) and NP-C publications (n = 9) were evaluated. Six non-systematic literature review publications were also included. In general, published reports did not provide explicit descriptions of psychiatric symptoms. The literature search findings are presented with a didactic perspective, showing key features for each disease and psychiatric signs that should trigger psychiatrists to suspect that psychotic symptoms may be secondary to an IEM.

Conclusion: IEMs with a psychiatric presentation and a lack of, or sub-clinical, neurological signs are rare, but should be considered in patients with atypical psychiatric symptoms.


Figure 1
Figure 1
Summary of literature review process.
Figure 2
Figure 2
Diagnostic algorithm for diagnosing inborn errors of metabolism in patients with schizophrenia-like symptoms. Negative: If exams are negative and suspicion is high. Positive: Could lead to diagnoses or high suspicion of specific disease. MRI = magnetic resonance imaging; MTHFR-CbS = methylenetetrahydrofolate reductase-cystathionine beta-synthase; NP-C = Niemann-Pick disease type C; UCDs = urea cycle disorders, WD = Wilson disease.

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