Beta-ketothiolase deficiency

autorecessive

Beta-ketothiolase deficiency, also known as mitochondrial acetoacetyl-CoA thiolase (T2) deficiency or 2-methylacetoacetyl-CoA thiolase deficiency, is a rare metabolic disorder characterized by an inability to metabolize certain types of amino acids and ketones. This condition is part of a group of disorders known as organic acidemias. Beta-ketothiolase deficiency is caused by mutations in the ACAT1 gene, which encodes the mitochondrial enzyme acetoacetyl-CoA thiolase, essential for the breakdown of isoleucine, a type of amino acid, and the utilization of ketones, which are produced during periods of fasting or illness.

Symptoms and Diagnosis

The symptoms of beta-ketothiolase deficiency typically manifest during infancy or early childhood and can be triggered by periods of fasting, infections, or other stressors. These symptoms may include vomiting, dehydration, difficulty breathing, lethargy, and in severe cases, coma. If left untreated, the disorder can lead to developmental delay, seizures, and potentially life-threatening metabolic crises.

Diagnosis of beta-ketothiolase deficiency involves biochemical tests that detect elevated levels of specific organic acids in the urine. Genetic testing can confirm the diagnosis by identifying mutations in the ACAT1 gene.

Treatment and Management

The management of beta-ketothiolase deficiency focuses on preventing metabolic crises through a controlled diet that limits the intake of isoleucine and other problematic amino acids. During illness or other stressors, prompt medical intervention to prevent catabolism and the accumulation of toxic metabolites is critical. This may include intravenous glucose and electrolytes to maintain energy levels and hydration. In some cases, supplements of carnitine may be recommended to help remove excess organic acids from the body.

Prognosis

With early diagnosis and proper management, individuals with beta-ketothiolase deficiency can lead relatively normal lives. However, the risk of metabolic crises remains, and ongoing medical supervision is necessary to adjust dietary and treatment plans as needed.