Ornithine transcarbamylase deficiency, hyperammonemia due to

Ornithine Transcarbamylase Deficiency (OTCD) is a genetic disorder that affects the urea cycle, a series of biochemical processes in the liver responsible for removing ammonia from the bloodstream. Ammonia is a toxic byproduct of protein metabolism, and its accumulation in the body can lead to serious health issues, including hyperammonemia, brain damage, and in severe cases, death. OTCD is caused by mutations in the OTC gene, which encodes the enzyme ornithine transcarbamylase, crucial for the effective functioning of the urea cycle.

Symptoms and Diagnosis

Symptoms of OTCD can vary widely among individuals, ranging from mild to severe. In newborns, symptoms often appear in the first few days of life and may include poor feeding, vomiting, lethargy, and seizures. If left untreated, these symptoms can rapidly progress to more severe complications such as coma and neonatal death. In less severe cases, or in individuals with late-onset OTCD, symptoms may not appear until later in life and can be triggered by dietary protein intake or stressful events. These symptoms include confusion, headache, ataxia (lack of muscle coordination), and hyperammonemic encephalopathy.

Diagnosis of OTCD involves a combination of clinical evaluation, biochemical tests (including blood ammonia and amino acid levels), and genetic testing to identify mutations in the OTC gene.

Treatment and Management

The primary goal of treatment for OTCD is to manage ammonia levels within the body. This is typically achieved through dietary restrictions to limit protein intake and the administration of medications that help to remove ammonia from the bloodstream. In acute cases, hemodialysis may be necessary to rapidly reduce ammonia levels. Long-term management may include the use of nitrogen-scavenging drugs, such as sodium benzoate or sodium phenylbutyrate, which help to eliminate ammonia via alternative pathways.

Liver transplantation is considered a definitive treatment for OTCD, as it replaces the defective enzyme with a functioning one, allowing for normal urea cycle function. However, this option is reserved for cases where medical management is not effective or for individuals with severe disease.

Genetics

OTCD is an X-linked genetic disorder, meaning the OTC gene is located on the X chromosome. As a result, the condition is more commonly and severely manifested in males, who have only one X chromosome. Females, having two X chromosomes, are often carriers of the disorder and may exhibit milder symptoms due to the presence of a normal copy of the OTC gene on their other X chromosome.

Epidemiology

OTCD is the most common urea cycle disorder, but it is still relatively rare, with an estimated incidence of 1 in 14,000 to 1 in 77,000 live births worldwide. The condition affects individuals of all ethnic backgrounds.

See Also

• Urea cycle disorder
• Hyperammonemia
• Genetic disorder
• Liver transplantation

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