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Hereditary urea cycle abnormality

Hereditary urea cycle abnormality is an inherited condition that can cause problems with the removal of waste from the body in the urine.

Alternative Names

Abnormality of the urea cycle - hereditary; Urea cycle - hereditary abnormality

Causes

The urea cycle is a process in which waste (ammonia) is removed from the body. When you eat proteins, the body breaks them down into amino acids. Ammonia is produced from leftover amino acids, and it must be removed from the body.

The liver produces several chemicals (enzymes) that change ammonia into a form called urea, which the body can remove in the urine. If this process is disturbed, ammonia levels begin to rise.

Several inherited conditions can cause problems with this waste-removal process. People with a urea cycle disorder are missing a gene that makes the enzymes needed to break down ammonia in the body.

These diseases include:

  • Argininosuccinic aciduria
  • Arginase deficiency
  • Carbamyl phosphate synthetase (CPS) deficiency
  • Citrullinemia
  • N-acetyl glutamate synthetase deficiency (NAGS)
  • Ornithine transcarbamylase deficiency (OTC)

As a group, these disorders occur in 1 in 30,000 newborns. Ornithine transcarbamylase deficiency is the most common of these disorders.

Boys are more often affected by ornithine transcarbamylase deficiency than girls. Girls are rarely affected. Those girls who are affected have milder symptoms and develop the disease later in life.

To get the other types of disorders, you need to receive a non-working copy of the gene from both parents. Sometimes parents don't know they carry the gene until their child gets the disorder.

Symptoms

Typically, the baby begins nursing well and seems normal. However, over time the baby develops poor feeding, vomiting, and sleepiness, which may be so deep that the baby is difficult to awaken. This usually occurs within the first week after birth.

Symptoms include:

  • Confusion
  • Decreased food intake
  • Dislike of foods that contain protein 
  • Increased sleepiness, difficulty waking up
  • Nausea, vomiting

Exams and Tests

The doctor will often diagnose these disorders when the child is still an infant.

Signs may include:

  • Abnormal amino acids in blood and urine
  • Abnormal level of orotic acid in blood or urine
  • High blood ammonia level
  • Normal level of acid in blood

Tests may include:

  • Genetic tests
  • Liver biopsy
  • MRI or CT scan

Treatment

Limiting protein in the diet can help treat these disorders by reducing the amount of nitrogen wastes the body produces. Special low-protein infant and toddler formulas are available.

It is important that a health care provider guide protein intake. The health care provider can balance the amount of protein so that the baby has enough to grow, but not enough to cause symptoms.

It is extremely important for people with these disorders to avoid fasting.

People with urea cycle abnormalities must also be very careful under times of stress, such as when they have infections. Stress, such as a fever, can cause the body to break down its own proteins. These extra proteins can make it difficult for the abnormal urea cycle to remove the byproducts.

Develop a plan with your doctor for when you are sick to avoid all protein, drink high carbohydrate drinks, and get enough fluids.

Most patients with urea cycle disorders will need to stay in the hospital at some point. During such times, they may be treated with medicines that help the body remove nitrogen-containing wastes. Dialysis may help rid the body of excess ammonia during extreme illness.

Support Groups

National Urea Cycle Disorders Forum -- www.nucdf.org

Outlook (Prognosis)

How well patients do depends on:

  • Which urea cycle abnormality they have
  • How severe it is
  • How early it is discovered
  • How closely they follow a protein-restricted diet

Babies diagnosed in the first week of life and put on a protein-restricted diet right away do well.

Sticking to the diet can lead to normal adult intelligence. Repeatedly not following the diet or having stress-induced symptoms can lead to brain swelling and brain damage.

Major stresses, such as surgery or accidents, can be complicated for these patients. Extreme care is needed to avoid problems during such periods.

Possible Complications

  • Coma
  • Confusion and eventually disorientation
  • Death
  • Increases in blood ammonia level
  • Swelling of the brain

When to Contact a Medical Professional

If your child has a test that shows increased ammonia in the blood, have the child examined by a genetic or metabolic specialist. If there is a family history of urea cycle disorder, seek genetic counseling before trying to get pregnant.

A dietician is important to help plan and update a protein-restricted diet as the child grows.

Prevention

As with most inherited diseases, there is no way to prevent these disorders. Prenatal testing is available. Genetic testing before an embryo is implanted may be available for those using in vitro fertilization .

Teamwork between parents, the affected child, and doctors can help prevent severe illness.

References

Rezvani I, Yudkoff M. Urea cycle and hyperammonemia (arginine, citrulline, ornithine). In: Kliegman RM, Stanton BF, St. Geme J, Schor N, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 79.

Updated: 2/3/2014

Chad Haldeman-Englert, MD, FACMG, Wake Forest School of Medicine, Department of Pediatrics, Section on Medical Genetics, Winston-Salem, NC. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team.


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