Case Report
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Feb 16, 2023; 11(5): 1077-1085
Published online Feb 16, 2023. doi: 10.12998/wjcc.v11.i5.1077
Diagnosis of an intermediate case of maple syrup urine disease: A case report
Yun-Ting Lin, Yan-Na Cai, Tzer Hwu Ting, Li Liu, Chun-Hua Zeng, Ling Su, Min-Zhi Peng, Xiu-Zhen Li
Yun-Ting Lin, Yan-Na Cai, Li Liu, Chun-Hua Zeng, Ling Su, Min-Zhi Peng, Xiu-Zhen Li, Department of Genetics and Endocrinology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, Guangdong Province, China
Tzer Hwu Ting, Department of Paediatrics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
Author contributions: Li XZ designed the study; Li XZ and Liu L enrolled the family and collected the clinical data; Lin YT, Cai YN, Su L and Peng MZ performed the experiments; Lin YT and Cai YN analyzed the data; Li XZ, Lin YT, Ting TH and Zeng CH wrote the paper.
Supported by the Guangzhou Science Technology and Innovation Commission, No. 202102020133.
Informed consent statement: Written informed consent was obtained from the guardian for participation in this study.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiu-Zhen Li, MM, Chief Physician, Department of Genetics and Endocrinology, Guangzhou Women and Children’s Medical Center, No. 9 Jinsui Road, Guangzhou 510623, Guangdong Province, China. 13725100840@163.com
Received: September 20, 2022
Peer-review started: September 20, 2022
First decision: November 30, 2022
Revised: December 12, 2022
Accepted: January 19, 2023
Article in press: January 19, 2023
Published online: February 16, 2023
Processing time: 147 Days and 0 Hours
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.

CASE SUMMARY

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.

CONCLUSION

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.

Keywords: Maple syrup urine disease; BCKDHB gene; Branched-chain amino acids; Metabolic profiling; Genetic analysis; Case report

Core Tip: Clinical and metabolic screening is limited in identifying all patients with maple syrup urine disease (MSUD), especially those patients with mild phenotypes or are asymptomatic. Here we present the diagnostic process of an intermediate MSUD case with a mild phenotype, who was missed by metabolic profiling but identified by genetic analysis. This case suggests that genetic testing could contribute to the identification of non-classic mild MSUD cases and alerts clinicians to avoid missing these patients.