Branched-chain amino acid transferase 2 (BCAT2) deficiency : a case series and systematic review

Filipič, Maja (avtor), Remec, Žiga Iztok (avtor), Drole Torkar, Ana (avtor), Šuštar, Nataša (avtor), Čuk, Vanja (avtor), Rodaro, Chiara (avtor), Debeljak, Maruša (avtor), Mlinarič, Matej (avtor), Šikonja, Jaka (avtor), Bančič, Vesna (avtor), Kotnik, Primož (avtor), Battelino, Tadej (avtor), Žerjav-Tanšek, Mojca (avtor), Grošelj, Urh (avtor), Repič-Lampret, Barbka (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: BCAT2, branched-chain amino acids, antihistamine branched-chain amino acid transaminase, hypervalinemia, hyperleucine-isoleucinemia, insulin resistance, white matter abnormalities
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 10 str.
• Številčenje: Vol. 46 , art. 101291
• PID: 20.500.12556/RUL-183369
• UDK: 616.3
• ISSN pri članku: 2214-4269
• DOI: 10.1016/j.ymgmr.2026.101291
• COBISS.SI-ID: 265156867
• Datum objave v RUL: 12.06.2026

Gradivo je del revije

• Naslov: Molecular genetics and metabolism reports
• Založnik: Elsevier
• ISSN: 2214-4269
• COBISS.SI-ID: 520387097

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P3-0343
• Naslov: Etiologija, zgodnje odkrivanje in zdravljenje bolezni pri otrocih in mladostnikih