Summary about Disease
Ornithine transcarbamylase deficiency (OTCD) is a genetic disorder caused by a deficiency of the enzyme ornithine transcarbamylase. This enzyme is crucial for the urea cycle, a process that removes ammonia, a toxic waste product, from the body. Without sufficient OTCD, ammonia builds up in the blood, leading to hyperammonemia and potential brain damage. OTCD is the most common urea cycle disorder. It varies in severity, with some individuals experiencing symptoms shortly after birth (neonatal-onset) and others developing symptoms later in life (late-onset).
Symptoms
Symptoms vary based on the severity of the deficiency and the age of onset.
Neonatal-onset: Lethargy, poor feeding, vomiting, seizures, coma, respiratory distress. Can be life-threatening.
Late-onset: Aversion to protein-rich foods, cyclic vomiting, confusion, headaches, behavioral changes, ataxia (loss of coordination), and in severe cases, coma. Symptoms can be triggered by illness, stress, or high-protein meals.
Causes
OTCD is caused by mutations in the OTC gene, which provides instructions for making the ornithine transcarbamylase enzyme. The gene is located on the X chromosome. OTCD is inherited in an X-linked dominant pattern. Males who inherit the mutated gene will typically have severe symptoms. Females who inherit one mutated gene and one normal gene may have a range of symptoms from mild to severe, or they may be asymptomatic carriers. *De novo* mutations (new mutations in the gene) can also occur.
Medicine Used
Treatment aims to lower ammonia levels in the blood and prevent future build-up. Medications include:
Ammonia scavengers: Sodium benzoate, sodium phenylacetate, and sodium phenylbutyrate are used to bind to ammonia and allow it to be excreted through the urine.
L-arginine or L-citrulline: Help stimulate the urea cycle.
Nitrogen-free calorie source: Dextrose is administered to prevent protein catabolism, which contributes to ammonia production.
Liver transplant: In severe cases, liver transplantation can provide a functional OTC enzyme.
Is Communicable
No, OTCD is not communicable. It is a genetic disorder and cannot be spread from person to person.
Precautions
Dietary management: A low-protein diet is crucial to limit ammonia production. Consult with a metabolic dietitian for a tailored dietary plan.
Emergency treatment plan: Have a plan in place for managing hyperammonemic crises, including knowing when and where to seek immediate medical attention.
Genetic counseling: For families with a history of OTCD, genetic counseling can help assess the risk of passing the condition on to future generations.
Avoid fasting: Prolonged periods without food can trigger protein catabolism and ammonia build-up.
How long does an outbreak last?
An "outbreak" in the context of OTCD refers to a hyperammonemic crisis, which is a period of elevated ammonia levels in the blood leading to acute symptoms. The duration of a hyperammonemic crisis varies depending on the severity, promptness of treatment, and individual factors. Without treatment, a crisis can be fatal. With prompt and effective medical intervention, the crisis can be resolved within days.
How is it diagnosed?
Diagnosis typically involves:
Blood tests: To measure ammonia levels, amino acid levels, and liver function. Elevated ammonia levels are a key indicator.
Urine tests: To assess organic acid levels and other metabolites.
Genetic testing: To identify mutations in the OTC gene.
Enzyme assay: Can be performed on a liver biopsy (though less common now due to genetic testing availability) to directly measure OTC enzyme activity.
Newborn screening: In some regions, newborn screening may include testing for urea cycle disorders, including OTCD.
Timeline of Symptoms
Neonatal-onset: Symptoms typically appear within the first few days of life (24-72 hours after birth).
Late-onset: Symptoms can appear at any time during childhood or adulthood. They may be triggered by illness, stress, or high-protein meals. The onset may be gradual and cyclical, with periods of normal health interspersed with periods of symptoms.
Important Considerations
Lifelong management: OTCD requires lifelong monitoring and management, including dietary restrictions, medication, and regular follow-up with a metabolic specialist.
Carrier status in females: Females who carry one copy of the mutated gene may exhibit varying degrees of symptoms, or none at all. Determining carrier status is crucial for genetic counseling.
Early diagnosis and treatment: Early diagnosis and prompt treatment are critical to preventing brain damage and improving long-term outcomes.
Multidisciplinary care: Management of OTCD requires a multidisciplinary team, including metabolic specialists, dietitians, genetic counselors, and nurses.