Identification of Additional Cases of Severe Neonatal <scp>GABA</scp> ‐Transaminase Deficiency

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 <i>ABAT</i> 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 <i>ABAT</i> 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.