Department of Pediatric Endocrinology, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China.
Radiology Department, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China.
J Pediatr Endocrinol Metab. 2021 Dec 10;35(3):303-312. doi: 10.1515/jpem-2021-0672. Print 2022 Mar 28.
Maple syrup urine disease (MSUD) is a rare metabolic autosomal recessive disorder caused by deficiency of the branched-chain α-ketoacid dehydrogenase complex. Mutations in the , and genes are responsible for MSUD. This study presents the clinical and molecular characterizations of four MSUD patients.
Clinical data of patients were retrospectively analyzed, and genetic mutations were identified by whole-exome sequencing. CLUSTALX was employed to analyzed cross-species conservation of the mutant amino acid. The impact of the mutations was analyzed with PolyPhen-2 software. The I-TASSER website and PyMOL software were used to predict the protein three-position structure of the novel mutations carried by the patients.
Vomiting, irritability, feeding difficulties, seizures, dyspnoea, lethargy and coma were the main clinical presentations of MSUD. Cranial MRI showed abnormal symmetrical signals in accordance with the presentation of inherited metabolic encephalopathy. Seven mutations were detected in four patients, including three novel pathogenic mutations in the (c.656C>A), (deletion of a single-copy of ) and (c.1219dup) genes. Structural changes were compatible with the observed phenotypes.
Different types of MSUD can display heterogeneous clinical manifestations. Exhaustive molecular studies are necessary for a proper differential diagnosis. The newly identified mutation will play a key role in the prenatal diagnosis of MSUD in the future.
枫糖尿症（MSUD）是一种罕见的常染色体隐性遗传代谢疾病，由支链α-酮酸脱氢酶复合体缺陷引起。MSUD 由 、 和 基因突变引起。本研究介绍了 4 例 MSUD 患者的临床和分子特征。
回顾性分析患者的临床资料，采用全外显子组测序鉴定基因突变。使用 CLUSTALX 分析突变氨基酸的种间保守性。用 PolyPhen-2 软件分析突变的影响。使用 I-TASSER 网站和 PyMOL 软件预测患者携带的新型突变的蛋白三维结构。
呕吐、易激惹、喂养困难、癫痫发作、呼吸困难、嗜睡和昏迷是 MSUD 的主要临床表现。头颅 MRI 显示与遗传性代谢性脑病一致的异常对称信号。在 4 名患者中检测到 7 种突变，包括 （c.656C>A）、 （缺失一个拷贝）和 （c.1219dup）基因中的 3 种新的致病性突变。结构变化与观察到的表型一致。
不同类型的 MSUD 可表现出异质性的临床表现。彻底的分子研究对于正确的鉴别诊断是必要的。新发现的突变将在未来 MSUD 的产前诊断中发挥关键作用。
