Pediatrics Department, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Genetics Department, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Mol Genet Genomic Med. 2021 May;9(5):e1616. doi: 10.1002/mgg3.1616. Epub 2021 May 6.
Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by the deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes which encode the E1α, E1β, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD in a cohort of Chilean MSUD patients by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes and to describe their impact on the phenotypic heterogeneity of these patients.
This manuscript describes a cross-sectional study of 18 MSUD patients carried out using PCR and DNA sequencing.
Four novel pathogenic mutations were identified: one in BCKDHA (p.Thr338Ile), two in BCKDHB (p.Gly336Ser e p.Pro240Thr), and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously. There were no correlations between the genotype and phenotype of the patients.
If MSUD is diagnosed earlier, with a newborn screening approach, it might be possible to establish genotype-phenotype relationships more efficiently.
枫糖尿症（MSUD）是一种常染色体隐性遗传代谢疾病，由支链α-酮酸脱氢酶（BCKD）酶复合物活性缺乏引起。BCKD 是一种由四个基因编码的线粒体复合物：BCKDHA、BCKDHB、DBT 和 DLD。MSUD 主要由 BCKDHA、BCKDHB 和 DBT 基因的突变引起，这些基因分别编码 BCKD 复合物的 E1α、E1β 和 E2 亚基。本研究的目的是通过鉴定 BCKDHA、BCKDHB 和 DBT 基因中的点突变，来描述智利 MSUD 患者队列的遗传基础，并描述它们对这些患者表型异质性的影响。
本研究采用 PCR 和 DNA 测序，对 18 例 MSUD 患者进行了横断面研究。
鉴定出 4 种新的致病性突变：一种在 BCKDHA 中（p.Thr338Ile），两种在 BCKDHB 中（p.Gly336Ser 和 p.Pro240Thr），一种在 DBT 中（p.Gly406Asp）。本研究还发现了另外 4 种致病性突变，这些突变之前已经有过描述。患者的基因型和表型之间没有相关性。
如果采用新生儿筛查方法更早地诊断 MSUD，则可能更有效地建立基因型-表型关系。
