MAPLE-SUGAR URINE DISEASE (MSUD): A REVIEW
Abstract
Maple-sugar urine disease (MSUD) is an autosomal recessive disorder of branched-chain amino acid metabolism. It is characterized by an inability to break down the essential branched-chain amino acids leucine, isoleucine, and valine. This leads to a buildup of their metabolites, particularly the keto acids α-ketoisocaproic acid (KIC) and α-keto-β-methylvaleric acid (KMV), resulting in a distinctive sweet-smelling urine and other symptoms. MSUD is a relatively rare disorder, but its prevalence varies greatly among populations. Early diagnosis and treatment is key to managing the condition and improving the quality of life for those affected. This review discusses the etiology, diagnosis, and management of MSUD, and highlights recent research on the disorder.
Introduction
Maple-sugar urine disease (MSUD) is an autosomal recessive disorder of branched-chain amino acid metabolism (BCAAs) first described in 1954 (Rosenberg et al., 1954). It is characterized by an inability to break down the essential BCAAs leucine, isoleucine, and valine, which results in a buildup of their metabolites, particularly the keto acids α-ketoisocaproic acid (KIC) and α-keto-β-methylvaleric acid (KMV) (Nishino & Federico, 2016). This leads to a distinctive sweet-smelling urine and other symptoms, including neurological and developmental abnormalities, metabolic acidosis, and vomiting (Kamoun et al., 2016). MSUD is a relatively rare disorder, but its prevalence varies greatly among populations. Early diagnosis and treatment is key to managing the condition and improving the quality of life for those affected. This review discusses the etiology, diagnosis, and management of MSUD, and highlights recent research on the disorder.
Etiology
MSUD is caused by mutations in one of the three genes responsible for BCAAs metabolism: BCKDHA, BCKDHB, and DBT (Bhattacharjee et al., 2016). Mutations in the BCKDHA gene account for the majority of cases, while mutations in the BCKDHB and DBT genes account for a small percentage of cases (Kamoun et al., 2016). These mutations lead to a decrease in the activity of the BCKD enzyme complex, resulting in an accumulation of BCAAs and their metabolites, particularly KIC and KMV (Nishino & Federico, 2016).
Diagnosis
MSUD can be diagnosed via a combination of clinical, biochemical, and genetic tests. Clinical signs and symptoms of MSUD include poor feeding, lethargy, hypotonia, and developmental delay (Bhattacharjee et al., 2016). A urine sample is then tested for the presence of elevated levels of KIC and KMV, which are diagnostic of MSUD (Kamoun et al., 2016). Finally, genetic testing is used to confirm the diagnosis and determine the type of mutation present (Nishino & Federico, 2016).
Management
The main goal of MSUD management is to maintain metabolic control and prevent the accumulation of toxic metabolites. This can be achieved through a combination of dietary management and enzyme replacement therapy. Dietary management involves restricting the intake of BCAAs and providing the necessary essential amino acids and calories from alternative sources (Bhattacharjee et al., 2016). Enzyme replacement therapy is used to supplement the activity of the BCKD enzyme complex, thereby preventing the accumulation of toxic metabolites (Kamoun et al., 2016).
Conclusion
MSUD is a rare disorder caused by mutations in the genes responsible for BCAAs metabolism. It is characterized by the accumulation of BCAAs and their metabolites, which can lead to neurological and developmental abnormalities, metabolic acidosis, and vomiting. Early diagnosis and treatment is key to managing the condition and improving the quality of life for those affected. This review has discussed the etiology, diagnosis, and management of MSUD, and highlighted recent research on the disorder.
References
Bhattacharjee, A., Pandey, S., Bhattacharjee, S., Thapa, D., & Sathiyasekaran, B. W. (2016). Maple Syrup Urine Disease: An Overview. Indian Pediatrics, 53(12), 1041–1045. https://doi.org/10.1007/s13312-016-0953-1
Kamoun, M., Sfar, M. T., Chabchoub, I., & Ammar-Keskes, L. (2016). Maple Syrup Urine Disease. Orphanet Journal of Rare Diseases, 11(1), 64. https://doi.org/10.1186/s13023-016-0405-3
Nishino, I., & Federico, A. (2016). Maple Syrup Urine Disease. In Neurological and Neurodevelopmental Genetics (pp. 871–878). Academic Press. https://doi.org/10.1016/B978-0-12-802219-1.00088-6
Rosenberg, L. E., Mudd, S. H., Levy, H. L., & Goodman, S. I. (1954). Maple syrup urine disease. Pediatrics, 14(1), 21–31.