Branched-chain keto acid dehydrogenase kinase deficiency

Branched-chain keto acid dehydrogenase kinase deficiency is a rare metabolic disorder that affects the body's ability to break down certain amino acids, specifically the branched-chain amino acids (BCAAs): leucine, isoleucine, and valine. These amino acids are essential components of proteins and play a crucial role in various bodily functions. The deficiency is caused by mutations in the gene responsible for encoding branched-chain keto acid dehydrogenase kinase (BCKDK), an enzyme that regulates the activity of the branched-chain keto acid dehydrogenase (BCKD) complex. The BCKD complex is essential for the catabolism of BCAAs. When BCKDK activity is deficient, the BCKD complex remains overly active, leading to an abnormal breakdown of BCAAs and their corresponding keto acids.

Symptoms and Diagnosis

The clinical presentation of individuals with branched-chain keto acid dehydrogenase kinase deficiency can vary widely. Symptoms may include developmental delay, seizures, hypotonia (reduced muscle tone), and failure to thrive in infancy or early childhood. Neurological issues, such as ataxia (lack of muscle coordination) and intellectual disability, may also occur. Diagnosis is typically made through biochemical analysis, which reveals elevated levels of BCAAs and their corresponding keto acids in the blood and urine. Genetic testing can confirm mutations in the BCKDK gene.

Treatment and Management

Management of branched-chain keto acid dehydrogenase kinase deficiency involves dietary restrictions to limit the intake of BCAAs. This dietary management must be carefully balanced to avoid malnutrition, as BCAAs are essential nutrients. In some cases, supplementation with thiamine (vitamin B1), which is a cofactor for the BCKD complex, may be beneficial. Regular follow-up with a metabolic specialist and a dietitian is essential to monitor the condition and adjust dietary intake as necessary.

Genetics

The condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected. Carriers, who have only one copy of the mutation, typically do not show symptoms of the disease.

Epidemiology

Branched-chain keto acid dehydrogenase kinase deficiency is considered a rare disease, with only a small number of cases reported in the medical literature. Due to its rarity, the exact prevalence is unknown.

See Also

• Metabolic disorder
• Amino acid metabolism disorder
• Genetic disorder
• Autosomal recessive inheritance

NIH genetic and rare disease info

• NIH info on Branched-chain keto acid dehydrogenase kinase deficiency

Branched-chain keto acid dehydrogenase kinase deficiency is a rare disease.