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

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

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.

• Language: English
• Keywords: BCAT2, branched-chain amino acids, antihistamine branched-chain amino acid transaminase, hypervalinemia, hyperleucine-isoleucinemia, insulin resistance, white matter abnormalities
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 10 str.
• Numbering: Vol. 46 , art. 101291
• PID: 20.500.12556/RUL-183369
• UDC: 616.3
• ISSN on article: 2214-4269
• DOI: 10.1016/j.ymgmr.2026.101291
• COBISS.SI-ID: 265156867
• Publication date in RUL: 12.06.2026

Record is a part of a journal

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

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P3-0343
• Name: Etiologija, zgodnje odkrivanje in zdravljenje bolezni pri otrocih in mladostnikih