Personalized medicine approach confirms a milder case of ABAT deficiency

“…The variant is pathogenic, resulting in the ABAT deficiency phenotype observed in our case. In comparison to the previous reports, 3,4,8,10,[12][13][14][15][16][17][18] our patient had a previously unreported homozygous missense mutation in the ABAT gene.…”

“…To date, only 14 patients worldwide have been reported in the published literature with GABA-T deficiency. 3 4 8 10 12 13 14 15 16 17 18 Six of these patients survived for more than 3 years, compared with the previously reported mortality rate within the first 2 years of life. 8 Our patient died at 30 months, which is consistent with previous data.…”

“…Recently flumazenil, a benzodiazepine antagonist, was administered in 1 patient who showed clinical improvement in seizure control, alertness, and adventitious movements with no adverse effects over a period of 11 months. 2,8 However, no benefit was noted in another reported case. 2,9 Flumazenil, being an antagonist of the benzodiazepine binding site of the GABA A receptor, was implemented as targeted therapy in an attempt to decrease GABAergic innervation.…”

“…Eight nonrecurrent, rare pathogenic or likely pathogenic CNVs that contained 1 or more genes associated with ID, autism, and seizures were identified (Table 2): 2p16.1-p15 duplication, 6p25.3-p25.1 duplication, 8p23.3p23.1 deletion, 9p24.3-p23 deletion, 10q11.22-q11.23 duplication, 12p13.33-13.2 duplication, 13q34 deletion, and 16p13.2 duplication. Four genes found in these CNVs may have had a role in patients’ neurodevelopment phenotype and had low RVISs as follows: 4-aminobutyrate aminotransferase ( ABAT ) (OMIM 137150), –0.33 (30.7% MIG); collagen, type IV, α-1 ( COL4A1 ) (OMIM 120130), –2.82 (0.6% MIG); calcium channel, voltage-dependent, L type, α-1C subunit ( CACNA1C ) (OMIM 114205), –2.09 (1.5% MIG); and SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 2 ( SMARCA2 ) (OMIM 600014), –1.97 (1.82% MIG).…”