Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Orphanet J Rare Dis. 2024 Oct 25;19(1):396. doi: 10.1186/s13023-024-03411-7.
Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by variants in any of the following genes: BCKDHA, BCKDHB, and DBT gene. Previous reports have highlighted a variety of common causing genes and variants among different ethnic groups affected by MSUD. This study is the first to describe the molecular characteristics, potential common variants, clinical phenotypes, and treatment outcomes of 20 Thai MSUD patients before the implementation of expanded newborn screening in Thailand.
A cross-sectional, multicenter study was conducted, including twenty Thai MSUD patients from 1997 to 2023. Most of the patients presented with classic neonatal onset (95%). The mortality rate was 20%, while global developmental delay was observed in 40% of the patients. Variants in the BCKDHB gene were detected in 85% (17/20) of the patients, while the BCKDHA gene accounted for 15% (3/20). The study identified the 11-kb deletion involving 5'UTR, exon 1, and intron 1 in the BCKDHB gene, from a position of g.80102385 to g.80113453 (NC_000006.12), accounting for 50% of all variants (20/40 alleles) in Thai MSUD patients. All patients with the 11-kb deletion in BCKDHB presented with the classic type. The gap-PCR for this common deletion was established in the study.
This study is the first to describe the clinical and molecular spectrum of Thai MSUD patients before the implementation of expanded NBS. The 11-kb deletion involving exon 1 in the BCKDHB emerges as the most common variant among Thai individuals with MSUD. Furthermore, the gap-PCR test for detecting the 11-kb exon 1 deletion status holds the potential for integration into stepwise molecular analysis following positive expanded newborn screening.
枫糖尿症（MSUD）是一种罕见的常染色体隐性遗传代谢疾病，由 BCKDHA、BCKDHB 和 DBT 基因中的任何一种变异引起。以前的报告强调了不同受 MSUD 影响的种族中存在多种常见的致病基因和变异体。本研究是泰国实施扩大新生儿筛查之前，首次描述 20 例泰国 MSUD 患者的分子特征、潜在常见变异体、临床表型和治疗结果。
进行了一项横断面、多中心研究，纳入了 1997 年至 2023 年的 20 例泰国 MSUD 患者。大多数患者表现为经典的新生儿发病（95%）。死亡率为 20%，而 40%的患者存在全面发育迟缓。在 20 例患者中，检测到 BCKDHB 基因的变异占 85%（17/20），而 BCKDHA 基因占 15%（3/20）。该研究发现了 BCKDHB 基因中的 11-kb 缺失，涉及 5'UTR、exon 1 和 intron 1，从 g.80102385 到 g.80113453（NC_000006.12），占泰国 MSUD 患者所有变异体（20/40 个等位基因）的 50%。所有 BCKDHB 基因 11-kb 缺失的患者均表现为经典型。在研究中建立了用于检测这种常见缺失的 gap-PCR。
本研究是泰国实施扩大新生儿筛查之前，首次描述 MSUD 患者的临床和分子谱。BCKDHB 基因 exon 1 中的 11-kb 缺失是泰国 MSUD 患者中最常见的变异体。此外，检测 11-kb exon 1 缺失状态的 gap-PCR 检测具有在阳性扩大新生儿筛查后纳入逐步分子分析的潜力。
