Inborn errors of metabolism associated with psychosis: literature review and case–control study using exome data from 5090 adult individuals

  • Yannis J. Trakadis
  • Vanessa Fulginiti
  • Mark Walterfang
Original Article
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Abstract

A literature review was conducted, using the computerized “Online Mendelian Inheritance in Man” (OMIM) and PubMed, to identify inborn errors of metabolism (IEM) in which psychosis may be a predominant feature or the initial presenting symptom. Different combinations of the following keywords were searched using OMIM: “psychosis”, “schizophrenia”, or “hallucinations” and “metabolic”, “inborn error of metabolism”, “inborn errors of metabolism”, “biochemical genetics”, or “metabolic genetics”. The OMIM search generated 126 OMIM entries, 40 of which were well known IEM. After removing IEM lacking evidence in PubMed for an association with psychosis, 29 OMIM entries were identified. Several of these IEM are treatable. They involve different small organelles (lysosomes, peroxisomes, mitochondria), iron or copper accumulation, as well as defects in other met-abolic pathways (e.g., defects leading to hyperammonemia or homocystinemia). A clinical checklist summarizing the key features of these conditions and a guide to clinical approach are provided. The genes corresponding to each of these con-ditions were identified. Whole exome data from 2545 adult cases with schizophrenia and 2545 unrelated controls, accessed via the Database of Genotypes and Phenotypes (dbGaP), were analyzed for rare functional variants in these genes. The odds ratio of having a rare functional variant in cases versus controls was calculated for each gene. Eight genes are significantly associated with schizophrenia (p < 0.05, OR >1) using an unselected group of adult patients with schizophrenia. Increased awareness of clinical clues for these IEM will optimize referrals and timely metabolic interventions.

Keywords

Maple Syrup Urine Disease Urea Cycle Disorder Propionic Acidemia Wolfram Syndrome Acute Intermittent Porphyria 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Notes

Acknowledgements

Data used in the preparation of this manuscript were obtained from the Database of Genotypes and Phenotypes (dbGaP) after McGill IRB approval. Raw data used is available in study phs000473.v1.p1. We thank the authors and dbGaP for access to the WES data. We thank Alexandre Dionne Laporte and Dr. G.Rouleau for bioinformatics support. We finally thank Bill Qi for developing the scripts and the Montreal Children’s Hospital Foundation for its financial support.

Compliance with ethical standards

Conflict of interest

Yannis J. Trakadis, Vanessa Fulginiti, and Mark Walterfang declare that they have no conflict of interest.

Studies with human or animal

This article does not contain any studies with human or animal subjects performed by any of the authors.

Supplementary material

10545_2017_23_MOESM1_ESM.doc (52 kb)
ESM 1 (DOC 51 kb)

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Copyright information

© SSIEM 2017

Authors and Affiliations

  • Yannis J. Trakadis
    • 1
  • Vanessa Fulginiti
    • 1
  • Mark Walterfang
    • 2
    • 3
  1. 1.Department of Medical GeneticsMcGill University Health CentreMontrealCanada
  2. 2.Department of NeuropsychiatryRoyal Melbourne HospitalMelbourneAustralia
  3. 3.Melbourne Neuropsychiatry CentreUniversity of MelbourneMelbourneAustralia

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