Branched-chain amino acid transferase type 2 (BCAT2) deficiency: Report of an eighth case and literature review
Branched-chain amino acid transferase type 2 (BCAT2) deficiency is a rare autosomal recessive genetic condition, with only seven cases described to date. It results in an elevation of branched-chain amino acid (BCAA) plasma concentrations, predominantly on valine, with normal concentration of plasma...
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Elsevier
2025-06-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221442692500028X |
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| author | Etienne Mondésert Juliette Bouchereau Manuel Schiff Jean-François Benoist Guilia Barcia Boris Keren Inès Mannes Clément Pontoizeau Charlotte Mansat Apolline Imbard |
| author_facet | Etienne Mondésert Juliette Bouchereau Manuel Schiff Jean-François Benoist Guilia Barcia Boris Keren Inès Mannes Clément Pontoizeau Charlotte Mansat Apolline Imbard |
| author_sort | Etienne Mondésert |
| collection | DOAJ |
| description | Branched-chain amino acid transferase type 2 (BCAT2) deficiency is a rare autosomal recessive genetic condition, with only seven cases described to date. It results in an elevation of branched-chain amino acid (BCAA) plasma concentrations, predominantly on valine, with normal concentration of plasma allo-isoleucine and urine branched-chain α-keto acids (BCKA). Despite this constant biochemical feature, clinical consequences remain unclear with heterogeneous and far less severe than maple syrup urine disease (MSUD) reported phenotypes, one individual being even asymptomatic.We report herein the eighth case of genetically confirmed BCAT2 deficiency, accompanied by a literature review and a discussion about the potential pathogenicity of this condition.An 11-year-old boy presented with a rapidly reversible initial acute neurological episode suggesting an epileptic seizure. Abnormalities on cerebral magnetic resonance imaging and suspicion of cognitive impairment led to further metabolic investigations. BCAT2 deficiency has been mentioned in front of increased BCAAs (valine = 1667 μmol/L, leucine = 701 μmol/L, isoleucine = 561 μmol/L). A homozygous novel nonsense variant on BCAT2 (c.34C > T, p.Arg12*) was found on whole exome sequencing. After oral pyridoxine supplementation (200 mg/day), a decrease in BCAA concentrations was observed (valine = 984 μmol/L, leucine = 462 μmol/L, isoleucine = 302 μmol/L).Laboratory and imaging findings were consistent with previously reported cases. However, clinical presentation of this case was atypical and could be related with epilepsy, although no other variant on epilepsy genes have been found. The relation between BCAT2 deficiency and these clinical findings is at this stage debated with regard to phenotypic variability. Further case-studies are needed to expand the knowledge about this condition. |
| format | Article |
| id | doaj-art-33873ea4e323416a906998bae4161bb3 |
| institution | OA Journals |
| issn | 2214-4269 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj-art-33873ea4e323416a906998bae4161bb32025-08-20T02:35:47ZengElsevierMolecular Genetics and Metabolism Reports2214-42692025-06-014310121310.1016/j.ymgmr.2025.101213Branched-chain amino acid transferase type 2 (BCAT2) deficiency: Report of an eighth case and literature reviewEtienne Mondésert0Juliette Bouchereau1Manuel Schiff2Jean-François Benoist3Guilia Barcia4Boris Keren5Inès Mannes6Clément Pontoizeau7Charlotte Mansat8Apolline Imbard9Department of Biochemistry, University Hospital of Montpellier, Montpellier, France; Corresponding author at: Department of Biochemistry, Lapeyronie Hospital, F34295 Montpellier, France.Reference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, FranceReference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris and Université Paris Cité, Paris, France; Inserm UMRS_1163, Institut Imagine, Paris, FranceDepartment of Biochemistry, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France and Université Paris-Saclay, Paris, FranceDepartment of Genetics, Necker-Enfants Malades Hospital, Assistance Publique Hospital of Paris, Paris, FranceDepartment of Genetics, La Pitié-Salpêtrière Hospital, Assistance Publique Hospital of Paris, Paris, France and Sorbonne University, Paris, FranceDepartment of Pediatric Radiology, AP-HP, Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, FranceInserm UMRS_1163, Institut Imagine, Paris, France; Department of Biochemistry, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France and Université Paris-Saclay, Paris, FranceDepartment of Pediatric Neurology, Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France and Department of General Pediatrics, Paris-Saclay Hospital, GHNE, Orsay, FranceDepartment of Biochemistry, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France and Université Paris-Saclay, Paris, FranceBranched-chain amino acid transferase type 2 (BCAT2) deficiency is a rare autosomal recessive genetic condition, with only seven cases described to date. It results in an elevation of branched-chain amino acid (BCAA) plasma concentrations, predominantly on valine, with normal concentration of plasma allo-isoleucine and urine branched-chain α-keto acids (BCKA). Despite this constant biochemical feature, clinical consequences remain unclear with heterogeneous and far less severe than maple syrup urine disease (MSUD) reported phenotypes, one individual being even asymptomatic.We report herein the eighth case of genetically confirmed BCAT2 deficiency, accompanied by a literature review and a discussion about the potential pathogenicity of this condition.An 11-year-old boy presented with a rapidly reversible initial acute neurological episode suggesting an epileptic seizure. Abnormalities on cerebral magnetic resonance imaging and suspicion of cognitive impairment led to further metabolic investigations. BCAT2 deficiency has been mentioned in front of increased BCAAs (valine = 1667 μmol/L, leucine = 701 μmol/L, isoleucine = 561 μmol/L). A homozygous novel nonsense variant on BCAT2 (c.34C > T, p.Arg12*) was found on whole exome sequencing. After oral pyridoxine supplementation (200 mg/day), a decrease in BCAA concentrations was observed (valine = 984 μmol/L, leucine = 462 μmol/L, isoleucine = 302 μmol/L).Laboratory and imaging findings were consistent with previously reported cases. However, clinical presentation of this case was atypical and could be related with epilepsy, although no other variant on epilepsy genes have been found. The relation between BCAT2 deficiency and these clinical findings is at this stage debated with regard to phenotypic variability. Further case-studies are needed to expand the knowledge about this condition.http://www.sciencedirect.com/science/article/pii/S221442692500028XBCAT2Branched-chain amino acidValinePyridoxineInborn error of metabolism |
| spellingShingle | Etienne Mondésert Juliette Bouchereau Manuel Schiff Jean-François Benoist Guilia Barcia Boris Keren Inès Mannes Clément Pontoizeau Charlotte Mansat Apolline Imbard Branched-chain amino acid transferase type 2 (BCAT2) deficiency: Report of an eighth case and literature review Molecular Genetics and Metabolism Reports BCAT2 Branched-chain amino acid Valine Pyridoxine Inborn error of metabolism |
| title | Branched-chain amino acid transferase type 2 (BCAT2) deficiency: Report of an eighth case and literature review |
| title_full | Branched-chain amino acid transferase type 2 (BCAT2) deficiency: Report of an eighth case and literature review |
| title_fullStr | Branched-chain amino acid transferase type 2 (BCAT2) deficiency: Report of an eighth case and literature review |
| title_full_unstemmed | Branched-chain amino acid transferase type 2 (BCAT2) deficiency: Report of an eighth case and literature review |
| title_short | Branched-chain amino acid transferase type 2 (BCAT2) deficiency: Report of an eighth case and literature review |
| title_sort | branched chain amino acid transferase type 2 bcat2 deficiency report of an eighth case and literature review |
| topic | BCAT2 Branched-chain amino acid Valine Pyridoxine Inborn error of metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S221442692500028X |
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