Summary about Disease
Ornithine transcarbamylase (OTC) deficiency is a genetic disorder that affects the urea cycle, a biochemical pathway that removes ammonia from the blood. In OTC deficiency, the enzyme ornithine transcarbamylase is either deficient or malfunctioning, leading to a buildup of ammonia in the bloodstream (hyperammonemia). This can cause serious neurological damage, coma, and even death, especially in newborns. It is the most common urea cycle disorder.
Symptoms
Symptoms vary depending on the severity of the deficiency and the age of onset. They can include:
Newborns: Lethargy, poor feeding, vomiting, rapid breathing, seizures, coma.
Older children and adults: Vomiting, confusion, irritability, headache, ataxia (lack of coordination), slurred speech, altered mental status, aversion to protein-rich foods. Mild cases may present later in life with cyclic vomiting or behavioral changes.
Causes
OTC deficiency is caused by mutations in the OTC gene, which provides instructions for making the ornithine transcarbamylase enzyme. Most cases are inherited in an X-linked recessive pattern. This means that males, who have only one X chromosome, will be affected if they inherit a mutated gene. Females, who have two X chromosomes, can be carriers (having one mutated gene and one normal gene) or can be affected if they inherit two mutated genes or if they have skewed X-inactivation favoring the mutated gene. Less commonly, new (de novo) mutations can occur in individuals with no family history of the disorder.
Medicine Used
Treatment focuses on lowering ammonia levels in the blood. Medications used include:
Ammonia-scavenging drugs: Sodium benzoate, sodium phenylacetate (or sodium phenylbutyrate) bind to waste products, allowing them to be excreted in the urine.
L-Arginine or L-Citrulline: Supplementation can help stimulate the urea cycle and promote ammonia detoxification.
Nitrogen-restricted diet: A diet low in protein is essential to reduce the production of ammonia.
Intravenous fluids and electrolytes: To correct dehydration and electrolyte imbalances.
Hemodialysis or hemofiltration: Used in severe cases to rapidly remove ammonia from the blood.
Liver transplantation: Considered in severe cases that are not responsive to other treatments.
Ravicti (glycerol phenylbutyrate) An oral liquid medication for long-term management.
Is Communicable
OTC deficiency is not communicable. It is a genetic disorder caused by a mutation in the OTC gene and cannot be spread from person to person.
Precautions
Genetic counseling: Families with a history of OTC deficiency should seek genetic counseling to understand the risk of recurrence in future pregnancies.
Newborn screening: Screening for OTC deficiency is included in newborn screening programs in some regions.
Dietary management: Strict adherence to a low-protein diet is crucial to prevent hyperammonemia.
Prompt treatment of hyperammonemic crises: Early recognition and treatment of hyperammonemic episodes are essential to prevent neurological damage.
Avoid fasting: Fasting can trigger hyperammonemia.
Avoid high-protein diets: High-protein diets can exacerbate the condition.
Monitor ammonia levels: Regular monitoring of blood ammonia levels is necessary to adjust treatment and diet.
How long does an outbreak last?
OTC deficiency is not an "outbreak" that resolves on its own. It is a chronic, lifelong condition. Episodes of hyperammonemia (high ammonia levels) can occur intermittently and last for days or weeks if not treated promptly. The duration of an episode depends on the severity of the deficiency, triggering factors, and the effectiveness of treatment.
How is it diagnosed?
Diagnosis typically involves:
Blood tests: Elevated ammonia levels, especially in the context of suggestive symptoms.
Urine tests: Elevated orotic acid levels (may be elevated, though not always).
Plasma amino acid analysis: May show characteristic patterns.
Genetic testing: Analysis of the OTC gene to identify mutations.
Liver biopsy: Enzyme assay to measure OTC activity (less commonly performed now due to availability of genetic testing).
Newborn Screening: Elevated glutamine or decreased citrulline on newborn screening can suggest the diagnosis.
Timeline of Symptoms
The timeline of symptoms varies greatly:
Neonatal-onset: Symptoms appear within the first few days of life. Rapid progression to lethargy, coma, and potentially death if not treated.
Late-onset (childhood or adulthood): Symptoms may be triggered by illness, stress, or high-protein intake. Onset can be gradual with intermittent episodes of vomiting, confusion, or behavioral changes. Diagnosis may be delayed.
Asymptomatic carriers (females): Some female carriers may remain asymptomatic throughout their lives, while others may experience mild symptoms, especially during times of stress.
Important Considerations
Lifelong management: OTC deficiency requires lifelong dietary management and monitoring.
Emergency preparedness: Patients and families should have a plan for managing hyperammonemic crises.
Psychological support: Coping with a chronic genetic disorder can be challenging, and psychological support may be beneficial.
Medication adherence: Strict adherence to prescribed medications is crucial for controlling ammonia levels.
Transition of care: As children with OTC deficiency grow into adulthood, it is important to ensure a smooth transition of care to adult healthcare providers who are knowledgeable about urea cycle disorders.
Pregnancy: Special considerations are necessary for women with OTC deficiency who are pregnant or planning to become pregnant, as pregnancy can increase the risk of hyperammonemia.
Vaccination: Vaccinations are essential and should be received as per normal schedule, to help avoid triggering catabolic states caused by infection.