In the brain, BCKAD helps metabolize BCAA to facilitate cerebral GABA and glutamate synthesis. The catabolism of these amino acids is necessary to maintain various physiologic functions such as : The branched-chain amino acids are essential amino acids with hydrophobic side chains and are found in protein-rich food. These intermediates are then converted into succinyl-CoA, acetoacetate, and acetyl-CoA. Consequently, alpha-ketoacids are further metabolized into intermediates such as isovaleryl-coenzyme A, alpha-methylbutyryl-CoA, and isobutyrl-CoA. Alpha-ketoacids are then oxidatively decarboxylated by the branched-chain ketoacid dehydrogenase complex. Their respective yielded alpha-ketoacids include alpha-ketoisocaproic acid, alpha-keto-beta-methyl valeric acid, and alpha-ketoisovaleric acid. Therefore, within the mitochondria, branched-chain amino acids are first converted into their respective alpha-ketoacids by the enzyme branched-chain amino acid transaminase. The activity of branched-chain ketoacid dehydrogenase is further regulated by BCKAD phosphatase and BCKAD kinase. The E3 subunit helps reoxidize the lipoic acid residue in E2. The lipoic acid residue in E2 transfers the acyl group from E1 to CoA. In the presence of thiamin pyrophosphate, E1 decarboxylates the alpha ketoacids. Together with branched-chain amino acid transaminase, it helps mediate catabolism of branched-chain amino acids (BCAA). It is composed of three catalytic subunits (E1, E2, and E3). Pathophysiologyīranched-chain ketoacid dehydrogenase (BCKAD) is located within the inner mitochondrial membrane of various tissues such as skeletal muscle, liver, kidney, and the brain. It can be estimated as 1 case per 71 births. In Portuguese gypsies, 1.4% of cases occur due to the homozygous deletion (117delC) of the BCKDHA gene. This is often termed as a founder's effect in the BCKDHA (E1a) gene (c.1312T>A). In Mennonites, maple syrup urine disease occurs with an incidence of 1 in 380 newborns. In the Ashkenazi Jewish population, the incidence is estimated at 1 in 26,000 live births. Higher occurrences have been noted in populations with a higher rate of consanguinity. It has an estimated worldwide incidence of 1 case per 185,000 live births. Maple syrup urine disease involves males and females equally. There are five main clinical phenotypes of maple syrup urine disease. The defect is transmitted in an autosomal recessive pattern. The metabolic disorder occurs due to a decreased activity of the branched-chain alpha-ketoacid dehydrogenase (BCKAD) complex which is located within the mitochondria. Furthermore, the E1 subunit is composed of E1alpha and two E1beta subunits. Two regulatory subunits (BCKAD kinase and BCKAD phosphatase) are also associated with the E2 subunit's core. These subunits include dihydrolipoamide dehydrogenase (E3 subunit) and BCKAD decarboxylase (E1 subunit) bound to dihydrolipoyl acyltransferase (E2 subunit). Etiologyįour subunits comprise the BCKAD multienzyme complex. Good clinical outcomes can be expected if management is initiated early. If left untreated, irreversible neurological damage and metabolic catastrophe ensue. Treatment consists of close metabolic monitoring and dietary restriction of branched-chain amino acids. It classically manifests in the neonatal period with failure to thrive, delayed developmental milestones, feeding difficulties, and a maple syrup odor in the urine or cerumen.
The underlying defect in the BCKAD complex disrupts the metabolism of branched-chain amino acids, which leads to an accumulation of branched-chain amino acids (BCAAs) in the plasma and their respective branched-chain ketoacids in the urine. This complex is responsible for the breakdown of branched-chain amino acids: It is a defect of metabolism due to abnormal activity of the branched-chain alpha-ketoacid dehydrogenase (BCKAD) complex.
Maple syrup urine disease (MSUD) was first described as a rapid onset of Menkes' neurodegenerative disease in 1954. Explain the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients with maple syrup urine disease.Review the management options available for maple syrup urine disease.Describe the pathophysiology of maple syrup urine disease.Outline the typical clinical presentation of a patient with maple syrup urine disease.This activity reviews the evaluation and management of maple syrup urine disease and highlights the interprofessional team's role in managing patients with this condition. Prompt diagnosis and treatment are necessary to prevent or reduce the severity of these complications. It can result in fatal irreversible neurocognitive deficits. Maple syrup urine disease is a rare, inborn error of metabolism, resulting in decreased branched-chain ketoacid dehydrogenase enzyme activity.
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