20.500.12556/DiRROS-25366 Branched-chain amino acid transferase 2 (BCAT2) deficiency a case series and systematic review Background: Branched-chain amino acid transaminase 2 (BCAT2) deficiency is an autosomal recessive disorder that impairs branched-chain amino acid (BCAA) catabolism. Its clinical and metabolic features remain poorly understood due to limited reports in the literature. Methods: We report three novel cases of BCAT2 deficiency from Slovenia: one diagnosed following symptom onset, one through cascade screening of parents, and one by newborn screening. Diagnosis was established through metabolic evaluation and confirmation of pathogenic variants in the BCAT2 gene. In addition, we performed a systematic review of all previously reported cases of BCAT2 deficiency. Results: All three patients were homozygous for the NM_001190.4:c.600C > A (p.Tyr200Ter) variant, with valine concentrations at presentation of 2093, 2589, and 794 μmol/L. Only one patient was symptomatic, presenting with headaches, developmental delay, and intellectual disability, while the remaining two were largely asymptomatic. Notably, insulin resistance was observed in one of the three patients and may be associated with elevated BCAA levels. Systematic literature review identified 8 additional cases of BCAT2 deficiency. Genetic variant c.600C > A was also found in two Pakistani individuals, while the remaining variants were each reported in only a single individual. The most common clinical characteristics were intellectual disability (55%), developmental delay and other neurological symptoms (36%). Abnormal white matter findings on MRI were observed in all patients who underwent imaging. BCAA levels decreased in all patients receiving pyridoxine supplementation; however, only 50% showed clinical improvement. Conclusion: BCAT2 deficiency displays marked interindividual heterogeneity, ranging from asymptomatic cases to severe neurological impairment, which renders its pathogenicity uncertain. BCAT2 branched-chain amino acids antihistamine branched-chain amino acid transaminase hypervalinemia hyperleucine-isoleucinemia insulin resistance white matter abnormalities true false true Angleški jezik Ni določen Neznano 2026-01-19 09:23:04 2026-01-19 09:23:05 2026-01-20 04:06:11 0000-00-00 00:00:00 2026 0 0 Nasl. z nasl. zaslona; Opis vira z dne 19. 1. 2026; str. 1-10 Vol. 46 [article no.] 101291 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.3 2214-4269 10.1016/j.ymgmr.2026.101291 265156867 RAZ_Filipic_Maja_2026.pdf RAZ_Filipic_Maja_2026.pdf 1 AC6AFBBD0A18CA58BA22FD402D4BB6C0 92a44af50050a6e927a3899d10ea906b6464e3edb5840f5ae5a4f9fa082266f4 a45ec5e2-f510-11f0-a15d-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=38397 https://www.sciencedirect.com/science/article/pii/S2214426926000030 0 62e396a7-f510-11f0-a15d-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=38396 Univerzitetni klinični center Ljubljana 0 0 0