Ornithine translocase

Ornithine translocase deficiency, also known as hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, is a rare inherited disorder that affects the urea cycle, a series of biochemical processes in the liver responsible for removing ammonia from the blood. This condition is characterized by elevated levels of ornithine, ammonia, and homocitrulline in the blood. Ornithine translocase, also known as the ornithine transporter, is crucial for the transport of ornithine from the cytoplasm into the mitochondria, where it is essential for the urea cycle and the biosynthesis of arginine, a vital amino acid.

Symptoms and Signs

Individuals with ornithine translocase deficiency typically present symptoms in infancy or early childhood, although onset may occur at any age. Symptoms are often triggered by episodes of illness, stress, or dietary protein intake and may include:

• Neurological disturbances
• Lethargy
• Vomiting
• Seizures
• Coma
• Cognitive delays
• Failure to thrive
• Liver dysfunction

Causes

Ornithine translocase deficiency is caused by mutations in the SLC25A15 gene, which encodes the ornithine transporter protein. This condition is inherited in an autosomal recessive pattern, meaning that both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Diagnosis

Diagnosis of ornithine translocase deficiency involves a combination of clinical evaluation, biochemical tests, and genetic testing. Biochemical tests measure the levels of ammonia, ornithine, and homocitrulline in the blood and urine. Genetic testing can confirm a diagnosis by identifying mutations in the SLC25A15 gene.

Treatment

There is no cure for ornithine translocase deficiency, but treatment is available to manage symptoms and prevent complications. Treatment strategies may include:

• A low-protein diet to reduce ammonia production
• Arginine or Citrulline supplementation to facilitate the removal of ammonia
• Medications to remove excess ammonia from the bloodstream
• Liver transplantation in severe cases

Prognosis

The prognosis for individuals with ornithine translocase deficiency varies. With early diagnosis and appropriate treatment, many individuals can lead relatively normal lives. However, without treatment, the condition can lead to intellectual disability, liver failure, and potentially life-threatening complications.

Epidemiology

Ornithine translocase deficiency is a rare disorder, with an estimated incidence of 1 in 78,000 births worldwide. However, the actual prevalence may be higher due to underdiagnosis or misdiagnosis.

See Also

• Urea cycle
• Inborn errors of metabolism
• Liver transplantation
• Genetic testing