The treatment of disorders related to the urea cycle is a lifelong process aimed at managing symptoms and doesn't cure the disorder. Strategies include monitoring ammonia levels using blood tests - serum and plasma levels – at regular intervals and using the results to optimize treatment methods.
Dietary management is key to restricting the level of ammonia produced in the body. Drugs and supplements are also used to remove excess ammonia from the blood. Development of a urea cycle disorder (UCD) treatment plan involves a dedicated medical team of doctors from diverse disciplines such as genetics, pediatrics, metabolism and nutrition.
Treatment with Drugs
Sodium phenylbutyrate or buphenyl is an ammonia scavenger that is widely used to treat UCDs. It provides alternative ammonia removal pathways and prevents hyperammonemia. Sodium benzoate is also used for continual ammonia removal from the bloodstream. Oral lactulose and neosporin can help prevent ammonia production by bacteria in the colon. Multivitamins, calcium and antioxidant supplements are also prescribed in many cases.
Pharmaceutical grade L-citrulline supplements are used for carbamoylphosphate synthetase (CPS) and ornithine transcarbamylase (OTC) deficiency and L-arginine is used in case of argininosuccinate synthase deficiency and citrullinemia to catalyze the enzymes in urea cycle and support optimum ammonia removal. Antacids are often used to relieve gastrointestinal side effects of these drugs such as acid reflux and stomach ache.
Prevention or control of UCD symptoms can be achieved by dietary restrictions. Dietary protein is closely monitored and protein restriction is advised while balancing protein, fats and carbohydrates in the diet to make sure essential amino acids are adequately ingested and calorie intake matches the energy requirements of the body. Children are treated with a low protein and high calorie diet that includes a lot of vegetables, fruits and other starchy foods that are high in calorie but low in protein.
Special formulas that are low in protein content are available for infants with this disorder. Amino acid formulas such as Cyclinex, EAA and UCD I&II provide almost half of the dietary protein requirement for a day. Calorie modules such as Prophree, Polycose and ModuCal are also prescribed along with amino acid formulas. Poorly feeding children with UCDs can benefit by feeding through a tube implanted surgically in the stomach or a tube inserted via the nose into the stomach. These tubes have been helpful in maintaining metabolic stability and minimizing hospital admissions of children with feeding issues.
When other treatment and management options fail, liver transplant is an option in case of CPS or OTC deficiency, as the urea cycle enzymes are produced in the liver. The pros and cons of transplant and the possible risks such as side effects of immunosuppressants should be discussed in detail with doctors before opting for liver transplant.
Except OTC deficiency, all other UCD are autosomal recessive disorders. OTC defect is X-linked and is found more in males. Females have 2 X chromosomes and hence most females affected by this gene mutation are carriers and are mostly asymptomatic. Only 15% of female carriers show symptoms especially during infection, after protein rich meals, post-partum, and with GI bleeding, all of which increases stress on the urea cycle. Severity of symptoms in female carriers largely depends on the extent of hepatocytes affected. Carrier testing can be done for all UCD disorders if family history indicates presence of mutation specific to the disease.
Educating parents of children with this disorder is important for them to recognize the symptoms of hyperammonemia and to take extra care in case of infection and stress when ammonia production in the body is increased.
In case of respiratory failure due to urea cycle disorder, mechanical ventilation is used to aid respiration.