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

Articles in Press

Document Type : review article

Authors

1 Department of Human Genetics, School of medicine, Mashhad University of medical sciences, Mashhad, Iran

2 Department of medical genetics, Mashhad University of medical sciences, Mashhad-Iran.

3 Akbar Children hospital, Mashhad University of medical sciences

10.22038/jpp.2026.95249.5642

Abstract

Maple Syrup Urine Disease (MSUD) is an autosomal recessive inborn error of branched-chain amino acid metabolism caused by deficiency of the branched-chain α-keto acid dehydrogenase (BCKDH) complex. While globally rare, MSUD prevalence is significantly elevated in populations with high consanguinity rates, including Iran. This narrative mini-review synthesizes current knowledge on the Iranian MSUD landscape, including 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

Journal of Pediatric Perspectives

Articles in Press, Accepted Manuscript
Available Online from 02 June 2026

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