Ornithine translocase deficiency

Ornithine translocase deficiency is a rare, inherited urea cycle disorder that causes toxic ammonia to accumulate in the blood, potentially leading to severe neurological damage.

Overview

Ornithine translocase deficiency is an inherited disorder that prevents the body from properly processing nitrogen, leading to a buildup of toxic ammonia. Because the nervous system is highly sensitive to ammonia, this accumulation can cause significant health problems. The condition is also known as HHH syndrome (hyperornithinemia-hyperammonemia-homocitrullinuria syndrome).

Symptoms

Severity and age of onset vary widely:

• Infantile Form: Symptoms appear within days of birth, including lethargy, refusal to eat, vomiting, breathing difficulties, seizures, and potential coma.
• Later-Onset Form: Symptoms may appear from childhood to adulthood and include episodes of vomiting, lethargy, problems with coordination (ataxia), vision problems, developmental delay, learning disabilities, and muscle stiffness (spasticity).

Causes

The disorder is caused by mutations in the SLC25A15 gene, which provides instructions for making the mitochondrial ornithine transporter 1 protein. This protein is essential for the urea cycle, a process that converts toxic nitrogen into urea for excretion. When this transporter is defective, ammonia accumulates in the bloodstream. The condition is classified as a urea cycle disorder.

Inheritance

This condition is inherited in an autosomal recessive pattern. Both copies of the gene in each cell must have mutations for the disorder to occur. Parents of an affected individual typically carry one copy of the mutated gene but remain asymptomatic.