Abnormality of the urea cycle - hereditary

Definition

The urea cycle is a metabolic process in which waste (nitrogen) from the breakdown of dietary proteins is incorporated by the liver into a form (called urea) that can be excreted from the body in the urine.

Several hereditary conditions can cause problems with this waste-removal process. These are genetic diseases caused by the lack of a gene that makes critical enzymes needed for the urea cycle. They include:

• ornithine transcarbamylase deficiency (OTC)
• citrullinemia
• arginase deficiency
• argininosuccinic aciduria
• carbamyl phosphate synthetase (CPS) deficiency
• N-acetyl glutamate synthetase deficiency (NAGS)

Alternative Names

Causes

As a group, these disorders occur in 1 in 30,000 newborns. All are genetic diseases associated with lack of a protein/enzyme activity in the urea cycle. Ornithine transcarbamylase deficiency is the most common.

Ornithine transcarbamylase deficiency is an X-linked recessive disorder (which means that all boys who inherit one bad copy of the gene will have the disease). Girls are rarely affected, and those who are have milder symptoms and later onset.

The other types are inherited in an autosomal recessive manner, meaning that you need to get bad copies of the gene from both parents to develop the condition. Thus, the disorders can appear in families with no prior knowledge that the parents were carriers.

As a result of these disorders, ammonia levels rise as proteins are not properly broken down into urea and removed. If ammonia rises too high in the body it can cause symptoms, such as confusion. Untreated, this can progress to swelling of the brain, coma, and death.

These disorders are frequently diagnosed in infancy. Typically, the baby begins nursing well and seems normal. However, with time there is progressively poorer feeding, vomiting, and sleepiness which may be so deep that the baby is difficult to arouse.

Symptoms

• disliking protein-containing foods
• decreased food intake
• nausea, vomiting
• change in clarity of mind, confusion
• increased sleepiness, difficulty arousing person
• coma

Exams and Tests

• elevated blood ammonia level
• abnormal pattern of blood and urine amino acids
• abnormal level of orotic acid in blood or urine
• normal level of acid in blood
• low level of enzyme activity in liver biopsy
• abnormal genetic test result, mutation(s) present in one of the genes for the proteins of the urea cycle
• MRI or CT scan may show swelling of brain

Treatment

The mainstay of treatment of these disorders is PROTEIN RESTRICTION. As protein is the source of nitrogen-containing chemicals in the diet, limiting protein will limit the amount of nitrogen-wastes.

This reduces the stress on the hampered urea cycle. It is imperative that protein restriction be done with guidance from a health care professional who can make certain to balance the amount of protein needed for growth with that which will cause symptoms.

It is extremely important for people with these disorders to AVOID FASTING.

Patients with urea cycle abnormalities must also be very careful under times of stress, such as infections. Stress, such as fever, can cause the body to break down its own proteins and exceed the capacity of the abnormal urea cycle to dispose of the by-products.

A sick-day plan should be formulated with your doctor to avoid all protein, consume high carbohydrate drinks, and stay hydrated.

Most patients with urea cycle disorders require hospitalization at some point. During such times, they may be treated with medicines that help the body dispose of nitrogen-containing wastes. Dialysis may be required to help rid the body of excess ammonia during extreme illness.

Support Groups

NATIONAL UREA CYCLE DISORDERS FOUNDATION

4841 Hill Street; La Canada, CA 91011

Phone: 818-790-2460

Toll-Free: 1-800-38-NUCDF

www.nucdf.org

Outlook (Prognosis)

The outcome depends on which of the urea cycle abnormalities a person has, how severe it is, how early it is discovered, and how closely the protein-restricted diet is followed. Babies diagnosed in the first week of life and immediately placed on a protein-restricted diet do well.

Continued adherence to the diet can lead to normal adult intelligence. Repeated episodes of not following the diet or stress-induced symptoms can lead to repeated brain swelling and irreversible brain damage.

It should be expected that major stresses, such as surgery or accidents, can be complicated for these patients. Extreme care is required to avoid problems during such periods.

Possible Complications

• confusion progressing to disorientation
• coma
• death
• repeated increases in blood ammonia level

When to Contact a Medical Professional

If your child has a test that shows increased ammonia in the blood, request an evaluation by a biochemical geneticist or metabolic specialist. If there is a family history of urea cycle disorder, seek genetic counseling during family planning. A dietician is instrumental in planning and updating a protein-restricted diet as a child grows.

Prevention

As with most inherited diseases, there is no way to absolutely prevent these disorders. Prenatal testing is available. Preimplantation genetic testing may be available for those using in vitro fertilization.

Preventing episodes of severe illness, for example -- requiring hospitalization at times of stress, can often be managed by teamwork between parents, the affected child, and doctors.