Holocarboxylase synthetase

Holocarboxylase Synthetase Deficiency is a rare, inherited metabolic disorder characterized by the body's inability to effectively use the vitamin biotin due to a deficiency in the enzyme holocarboxylase synthetase (HCS). This enzyme is crucial for incorporating biotin into carboxylases, which are enzymes that play a vital role in various metabolic pathways, including the metabolism of fats, carbohydrates, and proteins. The condition is autosomal recessive, meaning that it occurs when an individual inherits two copies of the defective gene, one from each parent.

Symptoms and Diagnosis

The symptoms of holocarboxylase synthetase deficiency typically appear in the early months of life and can include hypotonia (decreased muscle tone), skin rash, alopecia (hair loss), seizures, ataxia (lack of muscle coordination), metabolic acidosis (increased acidity in the blood), and developmental delay. If left untreated, the condition can lead to coma and death. Diagnosis is based on clinical presentation, biochemical tests showing elevated levels of certain organic acids in the urine (organic aciduria), and genetic testing confirming mutations in the HLCS gene, which codes for the holocarboxylase synthetase enzyme.

Treatment

The primary treatment for holocarboxylase synthetase deficiency is lifelong supplementation with high doses of biotin, a B vitamin. Biotin supplementation can significantly improve symptoms and prevent further complications. Early diagnosis and treatment are critical for preventing irreversible damage. Regular follow-up with a metabolic specialist is recommended to monitor the condition and adjust treatment as necessary.

Genetics

Holocarboxylase synthetase deficiency is caused by mutations in the HLCS gene located on chromosome 21q22.1. This gene provides instructions for making the enzyme holocarboxylase synthetase. Mutations in the HLCS gene reduce the activity of this enzyme, leading to insufficient levels of biotinylated carboxylases, which are essential for breaking down proteins, fats, and carbohydrates.

Epidemiology

Holocarboxylase synthetase deficiency is considered a very rare disorder, though its exact prevalence is unknown. Cases have been reported worldwide, with no known ethnic or gender predilection.

See Also

• Biotinidase deficiency
• Metabolic disorder
• Inborn errors of metabolism
• Organic acidemia