A Rare Case of GABA Transaminase Deficiency diagnosed by Trio-Based WES Analysis

초록

GABA transaminase (GABA-T) deficiency (OMIM 137150) is an ultra- rare AR disorder of GABA metabolism caused by a mutation in ABAT gene (16p13.2) mitochondrial 4-aminobutyrate aminotransferase (GABA-T). GABA is an inhibitory neurotransmitter and metabolized by GABA transaminase(GABA-T) and succinic semialdehyde dehydragenases (SSADH) (Fig 1). GABA T deficiency result in accumulate GABA and beta alanine in brain and manifest with various degrees of refractory seizure, hypotonia, hyperreflexia, intellectual disorder, hypersomnolence. We report a rare case of GABA transaminase deficiency diagnosed through trio-based whole exome sequencing (WES) analysis. The patient was a Yemeni male infant, born preterm in week 33(+1) by vaginal delivery with maternal polyhydramnios. The baby had Apgar score 4/5 and birth weight was 1610gm (13 centiles for gestation). He was the 6th child of consanguineous healthy Yemen parents. The mother parity was 13-6-0-7-5. Four sisters were normal. One brother died from respiratory difficulty during the neonatal period (Fig.2). On clinical exam, the baby was hypotonic with dysmorphic features consisting of a long neck, enlarged fontanel, and both club feet(Fig.3) Since birth, the baby had no self-respiration and spontaneous movement, progressing to encephalopathy and coma with myoclonic seizure. EEG showed electrical partial seizure and diffuse cerebral dysfunction. Brain USG & Brain CT revealed ventriculomegaly and diffuse increased echogenicity in both periventricular white matter(Fig.4) Additionally, the baby showed central diabetes insipidus. Tri-based whole exome sequence confirmed the presence of Likely pathogenic homozygous mutation in the ABAT gene with GABA-T deficiency. Both parents were heterozygous for the same mutation. (Table1) This is a case that involved the diagnosis of a rare neurometabolic disorder in one ofthe babies in the family and eventual genetic counseling of the family. The family has been offer