Next-generation sequencing may detect gene variants linked to psychosis metabolism error

Next-generation sequencing may help identify gene variants linked to inborn errors of metabolism among a subgroup of patients with psychosis, according to study results published in Journal of Psychiatric Research.

“Due to the rarity of the individual [inborn errors of metabolism], only few psychiatrists are aware of psychotic symptoms due to underlying diseases as [inborn errors of metabolism],” Nikita van de Burgt, of the department of psychiatry and neuropsychology at Maastricht University’s School for Mental Health and Neuroscience in the Netherlands, and colleagues wrote. “Therefore, patients with psychotic symptoms due to [inborn errors of metabolism] may be misdiagnosed and miss the opportunity to receive appropriate treatment.”

According to the researchers, inborn errors of metabolism can manifest later in life and are commonly characterized by neuropsychiatric problems, such as psychosis. In the current study, van de Burgt and colleagues sought to assess the potential effectiveness of screening patients who presented with a psychotic disorder for inborn errors of metabolism with a single blood sample analyzed via next-generation sequencing (NGS), to identify rare and treatable causes of psychotic disorders. They obtained blood samples from 60 patients who had a psychotic disorder and a duration of illness of less than 5 years and screened samples for 67 genes using the Illumina MiSeq NGS technique. They then compared findings of the sequencing to the human reference genome and classified variants according to the American College of Medical Genetics and Genomics classification.

Results showed six variants of class 4 (likely pathogenic) and class 5 (pathogenic) origin, all of which were heterozygous, which meant no patients appeared affected by an inborn error of metabolism. The researchers considered the participants of the control group as carriers only and no participants exhibited an inborn error of metabolism as an underlying disease according to this approach. However, van de Burgt and colleagues noted the potential usefulness of NGS for detecting gene variants linked to inborn errors of metabolism among an enriched subgroup of patients with psychosis.

“As screening for [inborn errors of metabolism] still requires invasive and time- consuming methods, this study showed that a NGS approach is a good, relatively cheap, alternative to using multiple blood samples, urine samples, cerebrospinal fluid and MRI scans to detect hetero- or homo-zygous variants of genes related to [inborn errors of metabolism],” the researchers wrote. “Consequently, the detection of [inborn errors of metabolism] may be limited to the use of only one blood sample in the future. Taken together, future research should focus on screening for genetic variants associated with [inborn errors of metabolism] in ‘enriched, high-risk’ patients with the use of NGS.”