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Case Reports
. 2023 Feb 16;11(5):1077-1085.
doi: 10.12998/wjcc.v11.i5.1077.

Diagnosis of an intermediate case of maple syrup urine disease: A case report

Yun-Ting Lin  1 , Yan-Na Cai  1 , Tzer Hwu Ting  2 , Li Liu  1 , Chun-Hua Zeng  1 , Ling Su  1 , Min-Zhi Peng  1 , Xiu-Zhen Li  3
Affiliations
Case Reports

Diagnosis of an intermediate case of maple syrup urine disease: A case report

Yun-Ting Lin et al. World J Clin Cases. .

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

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Conflict of interest statement

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
The pedigree and brain magnetic resonance imaging of the proband. A: The pedigree at diagnosis; B: The pedigree at last visit. The arrow indicates the proband. Filled symbol represents the patient, while half-filled symbol represents carrier; C-F: Brain magnetic resonance imaging (T2-weighted-FLAIR). Abnormal signal in the right frontal lobe, and increased symmetrical signals in the basal ganglia are present at 1 year and 3 mo of age (C) and 1 year and 7 mo of age (D), but not seen at 3 years and 5 mo of age (E) and 5 years of age (F). The yellow arrows indicate brain lesions.
Figure 2
Figure 2
The urinary organic acid chromatograms of the proband. A: The urinary organic acid chromatogram of a normal control; B-J: The urinary organic acid chromatograms of the proband at 8 mo, 1 year and 1 mo, 1 year and 7 mo, 2 years, 2 years and 5 mo, 3 years and 3 mo, 4 years and 10 mo, 5 years and 7 mo, and 6 years and 2 mo of age, respectively. Peak 1, internal standard; Peak 2, external standard; Peak 3, 2-OH-isovaleric acid; Peak 4 and 9, 3-OH-isovaleric acid; Peak 5, 2-OH-isocaproic acid; Peak 6, 2-keto-isocaproic acid; Peak 7 and 8, 2-keto-3-methylvaleric acid.
Figure 3
Figure 3
The sequencing diagrams of the enrolled family. The red arrow indicates the variant site.
See this image and copyright information in PMC

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