3-Hydroxyisobutyryl-CoA deacylase deficiency

A rare metabolic disorder affecting the breakdown of certain amino acids

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3-Hydroxyisobutyryl-CoA deacylase deficiency is a rare metabolic disorder that affects the body's ability to break down certain amino acids, specifically valine. This condition is caused by a deficiency in the enzyme 3-hydroxyisobutyryl-CoA deacylase, which is necessary for the proper metabolism of valine.

Pathophysiology

3-Hydroxyisobutyryl-CoA deacylase deficiency is an inborn error of metabolism that disrupts the normal breakdown of valine, an essential amino acid. The enzyme 3-hydroxyisobutyryl-CoA deacylase is responsible for converting 3-hydroxyisobutyryl-CoA to methacrylyl-CoA in the valine catabolic pathway. When this enzyme is deficient, toxic metabolites accumulate, leading to various clinical symptoms.

Genetics

This disorder is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the defective gene, one from each parent, to be affected. The gene responsible for this condition is located on chromosome 15 and is known as HIBCH.

Diagram showing the autosomal recessive inheritance pattern.

Clinical Features

Individuals with 3-hydroxyisobutyryl-CoA deacylase deficiency may present with a range of symptoms, including:

• Developmental delay
• Hypotonia
• Metabolic acidosis
• Failure to thrive
• Seizures

The severity of symptoms can vary widely among affected individuals.

Diagnosis

Diagnosis of 3-hydroxyisobutyryl-CoA deacylase deficiency is typically made through a combination of clinical evaluation, biochemical testing, and genetic testing. Elevated levels of certain metabolites in the blood and urine, such as 3-hydroxyisobutyric acid, can suggest the diagnosis. Genetic testing can confirm mutations in the HIBCH gene.

Treatment

There is currently no cure for 3-hydroxyisobutyryl-CoA deacylase deficiency. Treatment is primarily supportive and may include dietary management to limit the intake of valine and other branched-chain amino acids. Management of metabolic crises and symptomatic treatment of seizures and developmental delays are also important aspects of care.

Prognosis

The prognosis for individuals with 3-hydroxyisobutyryl-CoA deacylase deficiency varies depending on the severity of the condition and the effectiveness of management strategies. Early diagnosis and intervention can improve outcomes.

Related pages

• Metabolic disorder
• Amino acid metabolism
• Inborn error of metabolism
• Autosomal recessive disorder

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