title: Phenotyping GABA transaminase deficiency: a case description and literature review.
abstract: Gamma-aminobutyric acid transaminase (GABA-T) deficiency is an autosomal recessive disorder reported in only three unrelated families. It is caused by mutations in the ABAT gene, which encodes 4-aminobutyrate transaminase, an enzyme of GABA catabolism and mitochondrial nucleoside salvage. We report the case of a boy, deceased at 12 months of age, with early-onset epileptic encephalopathy, severe psychomotor retardation, hypotonia, lower-limb hyporeflexia, central hypoventilation, and rapid increase in weight and, to a lesser rate, length and head circumference. He presented signs of premature pubarche, thermal instability, and water-electrolyte imbalance. Serum total testosterone was elevated (43.3 ng/dl; normal range <16), as well as serum growth hormone (7.7 ng/ml; normal range <1). Brain magnetic resonance imaging (MRI) showed decreased myelination and generalized brain atrophy, later confirmed by post-mortem examination. ABAT gene sequencing was performed post-mortem, identifying a homozygous variant c.888G > T (p.Gln296His),not previously described. In vitro analysis concluded that this variant is pathogenic. The clinical features of this patient are similar to those reported so far in GABA-T deficiency. However, distinct mutations may have a different effect on enzymatic activity, which potentially could lead to a variable clinical outcome. Clinical investigation aiming for a diagnosis should not end with the patient's death, as it may allow a more precise genetic counselling for the family.
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal. pjplouro@gmail.com.
authors.forename: Pedro
authors.identifier: 0000-0002-8512-7582
authors.initials: P
authors.lastname: Louro
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: Lina
authors.initials: L
authors.lastname: Ramos
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: Conceição
authors.initials: C
authors.lastname: Robalo
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: Cândida
authors.initials: C
authors.lastname: Cancelinha
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dinis
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Veiga
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Pina
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: Olinda
authors.initials: O
authors.lastname: Rebelo
authors.affiliation: Metabolic Unit, Department of Clinical Chemistry, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ana
authors.initials: A
authors.lastname: Pop
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Diogo
authors.affiliation: Metabolic Unit, Department of Clinical Chemistry, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Gajja S
authors.initials: GS
authors.lastname: Salomons
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Garcia
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics
chemical_list: D000612:4-Aminobutyrate Transaminase