Maple Syrup Urine Disease in Iran: Genetic Landscape, National Guidelines, and Emerging Therapies – A Narrative Mini-Review

Document Type : review article

Authors

1 Genetics Department, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Clinical Research Development Unit of Akbar Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Maple Syrup Urine Disease (MSUD) is an autosomal recessive inborn error of branched-chain amino acid metabolism caused by a deficiency of the branched-chain α-keto acid dehydrogenase (BCKDH) complex. Although globally rare, MSUD prevalence is significantly elevated in populations with high consanguinity rates, including Iran. This narrative mini-review synthesizes current knowledge of the Iranian MSUD landscape, incorporating recent epidemiological data from expanded newborn screening programs, the unique mutational spectrum characterized by frequent novel mutations in the BCKDHA, BCKDHB, and DBT genes, and the newly published 2025 Comprehensive Iranian Guidelines for diagnosis and management. We further discuss conventional management strategies, the role of liver transplantation, and emerging therapeutic frontiers, including BCKDHA-BCKDHB digenic gene therapy and mRNA-based approaches. Recent preclinical studies demonstrate that gene therapy can restore metabolic homeostasis in animal models, offering hope for curative interventions. However, long-term risks-including immunogenicity, genotoxicity, and durability-remain to be addressed. This review provides a roadmap for clinicians and researchers managing MSUD in consanguineous populations and highlights priorities for future research in Iran.

Keywords

References

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Journal of Pediatric Perspectives
Volume 14, Issue 4
April 2026
Pages 20077-20086

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