The acute phase is characterized by diffuse edema and locally severe edema. Thus, amino acid synthesis is affected, resulting in brain edema and abnormal myelination. Some scholars believe that the accumulation of BCAA in the brain will inhibit the activity of pyruvate dehydrogenase and α-ketoglutarate dehydrogenase which destroy the citric acid cycle. The mechanism of brain damage in MSUD patients is still unclear. This myelin dysplasia is a secondary change of long-term exposure to BCAA. The abnormal MRI findings were mainly increased signal intensity in T2-weighted images of the midbrain, brainstem, thalamus and globus pallidus. Most adolescents and young adults with MSUD have different severity of magnetic resonance imaging (MRI) white matter changes. The last four types are also called delayed type. MSUD can be divided into five types according to the central brain injury and metabolic acidosis: classic type, intermediate type, intermittent type, thiamin (vitamin B1, VB1) active type and dihydrothioctinamide acyl dehydrogenase (E3) type. Metabolic acidosis is the main cause of death in the first year while survivors often suffer from mental retardation, spastic palsy, cortical blindness and other neurological disorders. Three MSUD genotypes have been identified to date based on the genes involved: subtype 1α mutation affecting the Eα (BCKDHA) gene, subtype 1β mutation Eβ (BCKDHB) and subtype II mutation E2 (DBT) gene. Dihydrolipoamide branched chain transacylase E2(DBT) encodes the transacylase (E2) subunit.
The BCKD complex is thought to be composed of a core of 24 transacylase (E2) subunits, and associated decarboxylase (E1), dehydrogenase (E3), and regulatory subunits. MSUD is a rare genetic disorder which manifested as impaired branched-chain amino acid (BCAA) metabolism caused by branched-chain α-ketoacid dehydrogenase (BCKD) complex deficiency. Maple syrup urine disease (MSUD) was first reported by pediatrician Menkes in 1954, as the α-ketoacid excreted in urine smells like maple syrup.
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