Urea Cycle Disorder

Urea Cycle Disorder is a genetic defect. Babies born with this defect, liver fails to produce, all the six enzymes, which metabolizes protein. One of the most common types of Urea cycle disorder occurs, when one of these enzymes is deficient called Ornithine Transcarbamylase (OTC). This enzyme’s ability is to combine a molecule named ornithine with molecule named carbamoyl phosphate to make cirtulline (The first step in the urea cycle). If the enzyme is missing or not working properly the urea cycle does not work correctly and ammonia builds up in the body. A normal urea cycle (In the liver cells) occurs when nitrogen is turned into urea by enzymes, which is flushed out of the body in the urine. However, if the urea is not working properly, the body cannot turn nitrogen into urea. Instead, it turns the nitrogen into ammonia. As a result, ammonia causes irreversible brain damage, coma and eventual death. Estimated, one in every 80, 000 births are born with Urea Cycle Disorder, in the United States. When the disorder is not diagnosed, those children will die. Treatment for UCD includes: Reduce the amount of protein a child consumes, administer medication which takes extra ammonia out of the body, and add arginnine or citrulline to help the body use protein. Final option is a liver transplant, which has proven to be most effective.

Many related symptoms associated to Urea Cycle Disorder. During infancy, first symptoms develop within 24 to 72 hours after feeding. The baby will become excessively sleepy, and may have seizures. Also, symptoms may include: vomiting, poor feeding, and enlarged liver. In older children, symptoms may include: seizures, hyperactivity, confusion, persistent vomiting, enlarged liver, and children may refuse to eat meat or products containing high protein content (milk, cheese, peanuts, etc.).

Diagnosis for Urea Cycle Disorder, have a blood test to check for high ammonia and amino acid levels. Confirmation of this disease by a liver biopsy (Low levels of enzyme activity), and other specific tests for UCD, including MRI and CT scan, which examines for any swelling of the brain, caused by the ammonia in the blood. Childhood episodes of hyperammonemia (high ammonia levels in the blood) attributed to viral illnesses including chickenpox, high-protein meals or exhaustion. Sometimes this disorder is misdiagnosed as Reye’s Syndrome (Brain damage and liver damage of unknown cause. This syndrome has been associated to the use of aspirin to treat chickenpox or influenza in children). If both parents carry the defective gene, following outcomes are likely: Twenty-five percent probability their child will develop the disorder, Fifty percent probability their child will receive one defective gene from one of the parents (Child will not show symptoms of the disorder, however will be a “carrier,”), and Twenty-five percent probability their child will be fortunate, receiving from both parents normal genes. Ornithine transcarbamlase is the most common type of urea cycle disorder, and more commonly inherited in boys from the DNA of the mother.

Treatment for Urea Cycle Disorder is a lifelong process to manage the condition, and currently has no cure. Hopefully, through gene therapy research will develop a cure. Frequent blood tests will monitor the level of ammonia levels. Specialists in the area of pediatrics, genetics and nutrition work to together to develop a child’s treatment plan. A combination of steps is recommended, which include: Maintaining a low protein and high-calorie diet (fruits, vegetables, and starches) however certain amount of protein is necessary to maintain adequate growth, which can be reduced as the child grows. Children with this disorder maybe referred to a child psychologist because of their behavior and eating problems. People with this disorder must avoid fasting. Medication is administered, which binds the ammonia and carriers it out in the urine. Amino acid supplements such as arginine or citrulline are added to the diet. These supplements make protein, which is important for growth and tissue repair. Buphenyl (Sold in Europe under the trade name Ammonaps) medication (Sodium phenylbutyrate tablets and powder) is available, as a maintenance therapy for urea cycle disorder. In1996, Buphenyl approved by the Food Drug Administration. Dr. Saul Brusilow, Professor of Pediatrics at John Hopkins University, developed this medication. In February 2005, Pharmaceutical Corporation Medicis announced approval by the Food and Drug Administration, sale of Ammonul, which is a combination containing sodium phenylacetate (10%) and sodium benzoate (10%), treating patients that lack the enzyme, which dangerously increases ammonia in the bloodstream. This allows the body to safely remove the nitrogen, before it turns into ammonia. The medication is administered intravenously, but must be diluted with ten percent dextrose injection. Ammonul was granted by the FDA as an orphan drug status with seven years of exclusivity treating Urea Cycle Disorder. Patients having advanced liver disease related to this disorder may require having a liver transplant. In some cases, babies born with this disorder may undergo a liver transplant soon after birth (Production of urea cycle enzymes takes place in the liver). Certainly, a liver transplant incurs risks, including complications and treatment of symptoms prior to receiving a donated liver. Liver transplants have been effective in reversing the symptoms of this disorder.

“The National Urea Cycle Disorders Foundation is a nonprofit organization dedicated to the identification, treatment and cure of urea cycle disorders. Our organization was formed in 1988 by a handful of parents whose children were affected in order to provide a primary resource of information and education to families and medical professionals, and to support and stimulate research on urea cycle disorders. The Foundation is operated and supported by the volunteer efforts of families with children suffering from UCD’s.” Mail Address: NUCDF 4841 Hill Street, La Canada, CA 91011 (1 – 800- 38 – NUCDF).