BCKDHA

BCKDHA

BCKDHA (Branched-Chain Ketoacid Dehydrogenase E1 Alpha Polypeptide) is a gene that encodes a protein component of the branched-chain alpha-keto acid dehydrogenase complex (BCKD complex). This complex is crucial for the catabolism of branched-chain amino acids (BCAAs) such as leucine, isoleucine, and valine. The BCKDHA gene is located on chromosome 19q13.2.

Function

The BCKDHA gene encodes the E1 alpha subunit of the BCKD complex, which is a mitochondrial enzyme complex. This complex catalyzes the oxidative decarboxylation of branched-chain alpha-keto acids, which are derived from the transamination of BCAAs. The proper function of this complex is essential for maintaining normal levels of BCAAs and their corresponding keto acids in the body.

Clinical Significance

Mutations in the BCKDHA gene can lead to a metabolic disorder known as Maple Syrup Urine Disease (MSUD). MSUD is characterized by the accumulation of BCAAs and their toxic by-products in the blood and urine, leading to symptoms such as poor feeding, vomiting, lethargy, and developmental delay. The disease is named for the distinctive sweet odor of the urine in affected individuals, reminiscent of maple syrup.

Genetic Mutations

Several mutations in the BCKDHA gene have been identified that result in MSUD. These mutations can lead to a deficiency in the E1 alpha subunit, impairing the function of the BCKD complex. The inheritance pattern of MSUD is autosomal recessive, meaning that an individual must inherit two defective copies of the gene to manifest the disease.

Diagnosis and Treatment

Diagnosis of MSUD is typically made through newborn screening programs that detect elevated levels of BCAAs in the blood. Confirmatory testing involves genetic analysis to identify mutations in the BCKDHA gene. Treatment involves dietary management to restrict the intake of BCAAs and prevent the accumulation of toxic metabolites. In some cases, liver transplantation may be considered.

Also see

• Branched-chain amino acids
• Maple Syrup Urine Disease
• Metabolic disorders
• Genetic mutations

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