MSUD is amenable to treatment through dietary restriction of BCAAs, and with early treatment, patients typically have good clinical outcomes. Patients with this disorder have elevations of branch chain ketoacids in the urine in addition to elevated BCAAs in the plasma. Pathogenic homozygous or compound heterozygous variants in BCKDHA (MIM #608348), BCKDHB (MIM #248611), DBT (MIM #248610), or DLD (MIM #238331), which form the catalytic subunits of BCKAD, can result in MSUD, which is characterized by neurological and developmental delay, encephalopathy, feeding problems, and a maple syrup odor to the urine. Maple syrup urine disease (MSUD, MIM #248600) is an autosomal recessive disease characterized by disruption of the normal activity of the branched-chain α-ketoacid dehydrogenase (BCKAD) complex, the second step in the catabolic pathway for the branched-chain amino acids (BCAAs) that include leucine, isoleucine, and valine. We review this disorder including its presentation, screening and clinical diagnosis, treatment, and other relevant aspects pertaining to the care of patients. Newborn screening for MSUD is now commonplace in the United States and is included on the Recommended Uniform Screening Panel (RUSP). Clinical outcomes are generally good in patients where treatment is initiated early. Treatment consists of dietary restriction of BCAAs and close metabolic monitoring. The classic presentation occurs in the neonatal period with developmental delay, failure to thrive, feeding difficulties, and maple syrup odor in the cerumen and urine, and can lead to irreversible neurological complications, including stereotypical movements, metabolic decompensation, and death if left untreated.
The disorder varies in severity and the clinical spectrum is quite broad with five recognized clinical variants that have no known association with genotype. Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by defects in the branched-chain α-ketoacid dehydrogenase complex, which results in elevations of the branched-chain amino acids (BCAAs) in plasma, α-ketoacids in urine, and production of the pathognomonic disease marker, alloisoleucine.
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