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Abstract：
BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive genetic disorder caused by defects in the catabolism of the branched-chain amino acids (BCAAs). However, the clinical and metabolic screening is limited in identifying all MSUD patients, especially those patients with mild phenotypes or are asymptomatic. This study aims to share the diagnostic experience of an intermediate MSUD case who was missed by metabolic profiling but identified by genetic analysis.
METHODS: This study reports the diagnostic process of a boy with intermediate MSUD. The proband presented with psychomotor retardation and cerebral lesions on magnetic resonance imaging scans at 8 mo of age. Preliminary clinical and metabolic profiling did not support a specific disease. However, whole exome sequencing and subsequent Sanger sequencing at 1 year and 7 mo of age identified bi-allelic pathogenic variants of the BCKDHB gene, confirming the proband as having MSUD with non-classic mild phenotypes. His clinical and laboratory data were retrospectively analyzed. According to his disease course, he was classified into an intermediate form of MSUD. His management was then changed to BCAAs restriction and metabolic monitoring conforming to MSUD. In addition, genetic counseling and prenatal diagnosis were provided to his parents.
CONCLUSIONS: Our work provides diagnostic experience of an intermediate MSUD case, suggesting that a genetic analysis is important for ambiguous cases, and alerts clinicians to avoid missing patients with non-classic mild phenotypes of MSUD.
METHODS: This study reports the diagnostic process of a boy with intermediate MSUD. The proband presented with psychomotor retardation and cerebral lesions on magnetic resonance imaging scans at 8 mo of age. Preliminary clinical and metabolic profiling did not support a specific disease. However, whole exome sequencing and subsequent Sanger sequencing at 1 year and 7 mo of age identified bi-allelic pathogenic variants of the BCKDHB gene, confirming the proband as having MSUD with non-classic mild phenotypes. His clinical and laboratory data were retrospectively analyzed. According to his disease course, he was classified into an intermediate form of MSUD. His management was then changed to BCAAs restriction and metabolic monitoring conforming to MSUD. In addition, genetic counseling and prenatal diagnosis were provided to his parents.
CONCLUSIONS: Our work provides diagnostic experience of an intermediate MSUD case, suggesting that a genetic analysis is important for ambiguous cases, and alerts clinicians to avoid missing patients with non-classic mild phenotypes of MSUD.
摘要：
背景：枫糖浆尿病（MSUD）是一种由支链氨基酸（BCAAs）分解代谢缺陷引起的常染色体隐性遗传疾病。然而,临床和代谢筛查在识别所有MSUD患者方面受到限制，尤其是那些轻度表型或无症状的患者。这项研究旨在分享中间MSUD病例的诊断经验，该病例因代谢分析而错过，但通过遗传分析鉴定。
方法：本研究报告了一名患有中级MSUD的男孩的诊断过程。先证者在8个月大的磁共振成像扫描中表现出精神运动发育迟缓和脑部病变。初步的临床和代谢分析不支持特定的疾病。然而,全外显子组测序和随后的Sanger测序在1岁和7个月龄时确定了BCKDHB基因的双等位基因致病变异体，确认先证者具有非经典轻度表型的MSUD。回顾性分析其临床和实验室资料。根据他的病程,他被归类为MSUD的中间形式。然后将他的管理更改为符合MSUD的BCAA限制和代谢监测。此外,为他的父母提供遗传咨询和产前诊断。
结论：我们的工作提供了中级MSUD病例的诊断经验，表明基因分析对于模棱两可的情况很重要，并提醒临床医生避免错过MSUD非经典轻度表型患者。
方法：本研究报告了一名患有中级MSUD的男孩的诊断过程。先证者在8个月大的磁共振成像扫描中表现出精神运动发育迟缓和脑部病变。初步的临床和代谢分析不支持特定的疾病。然而,全外显子组测序和随后的Sanger测序在1岁和7个月龄时确定了BCKDHB基因的双等位基因致病变异体，确认先证者具有非经典轻度表型的MSUD。回顾性分析其临床和实验室资料。根据他的病程,他被归类为MSUD的中间形式。然后将他的管理更改为符合MSUD的BCAA限制和代谢监测。此外,为他的父母提供遗传咨询和产前诊断。
结论：我们的工作提供了中级MSUD病例的诊断经验，表明基因分析对于模棱两可的情况很重要，并提醒临床医生避免错过MSUD非经典轻度表型患者。
