Psychiatric signs and symptoms in treatable inborn errors of metabolism

Abstract

Possible underlying organic causes of psychiatric symptoms can be overlooked in the clinical setting. It is important to increase awareness amongst psychiatric and neurological professionals with regard to certain inborn errors of metabolism as, in some cases, disease-specific therapies are available that can, for instance, treat underlying metabolic causes. The following article describes the basic pathophysiology, clinical and neurological features, and available diagnostic procedures of six treatable metabolic diseases that are associated with neuropsychiatric symptoms: Wilson’s disease, cerebrotendinous xanthomatosis, porphyrias, homocysteinemia, urea cycle disorders, and Niemann-Pick disease type C (NP-C). NP-C is taken as a particularly relevant example because, while it is traditionally considered to be a condition that presents with severe neurological and systemic manifestations in children, an increasing number of patients are being detected who have the adolescent- or adult-onset form, which is frequently associated with neuropsychiatric signs. A notable proportion of adult-onset cases have been reported where NP-C has mistakenly been diagnosed and treated as a psychiatric condition, usually based on patients’ initial presentation with psychotic or schizophrenia-like symptoms. Underlying organic causes of psychiatric disorders such as psychosis should be considered among patients with atypical symptoms and/or resistance to standard therapy. Alongside improved frameworks for additional multidisciplinary diagnostic work in patients with suspected organic disease, the development of convenient and affordable biochemical screening and/or diagnostic methods has enabled new ways to narrow down differential diagnoses.

Cytosolic Accumulation of L-Proline Disrupts GABA-Ergic Transmission through GAD Blockade

“…A subset of these diseases also manifests neuropsychiatric dysfunction (Rahman et al, 2013; Nia, 2014). Evidence supporting detailed mechanisms by which these accumulated small-molecule metabolites directly cause neuropsychiatric manifestations, however, has rarely been convincingly described (Rahman et al, 2013; Nia 2014). That both clinical pharmaceuticals and drugs of abuse can acutely cause psychosis in otherwise normal individuals suggests the possibility that pathological accumulation of certain endogenous small-molecule metabolites might likewise contribute to psychosis.…”

Clinical Spectrum and Genetic Variability in Bulgarian Patients with Niemann-Pick Disease Type C

“…Depressive syndrome, behavioral problems with aggressiveness and social isolation have also been described [19,20] .…”

The investigation of inborn errors of metabolism as an underlying cause of idiopathic intellectual disability in adults in Norway

“…Psychiatric symptoms as the presenting symptom of IEMs were the topic of six papers . In addition, an overview of IEMs presenting with behavioural problems are also offered at http://www.treatable-id.org .…”

“…Inborn errors of metabolism may present with psychiatric symptoms without neurological or somatic symptoms , and in recent years there have been several good overviews on the topic. Psychosis, autism and other behavioural symptoms may lead practitioners to consider an IEM . The paper of Sedel et al .…”