# Identification of Additional Cases of Severe Neonatal GABA‐Transaminase Deficiency

## TL;DR

This case report describes three siblings with severe GABA-T deficiency, a rare genetic disorder, and suggests urine GABA testing as a useful screening method.

## Contribution

The paper provides evidence of a founder effect in the Canadian Indigenous population and highlights urine GABA quantification as a potential screening tool.

## Key findings

- Three siblings were found to be homozygous for a nonsense variant in the ABAT gene.
- Urine GABA quantification is proposed as a reasonable and accessible screening test for GABA-T deficiency.
- A trial of flumazenil infusion showed subtle improvement in EEG patterns.

## Abstract

GABA‐transaminase (GABA‐T) deficiency is a rare disorder of GABA metabolism characterized by neonatal encephalopathy, epilepsy, hypotonia and intellectual disability. It is caused by biallelic pathogenic variants in the ABAT gene. We report a case of a newborn female born to a G10P5 mother, with abnormal fetal movements and polyhydramnios in utero. At birth, she presented with hypotonia, hypersomnolence, decreased level of consciousness, central hypoventilation, non‐epileptic myoclonus, seizures, and neurogenic diabetes insipidus. Brain MRI on day two of life showed partial cerebellar vermis agenesis and cerebellar hemispheric dysplasia. Her EEG demonstrated burst suppression. Family history was significant for two siblings with a similar neonatal course. On rapid whole exome sequencing she was found to be homozygous for a nonsense variant in the ABAT gene designated c.1278C>A, p.Tyr426*. Both of her affected siblings were also found to be homozygous for the same variant, and carrier status was confirmed in both parents. A trial of flumazenil infusion showed subtle EEG improvement. Our report of three siblings with severe GABA‐T deficiency provides evidence for founder effect in the Canadian Indigenous population and discusses the utility of urine GABA quantification as a reasonable screening test.

A case report showing that GABA‐T deficiency can present quite severely in neonates with early lethality and there may be utility in using urine GABA quantification as a readily accessible screening test.