Inborn errors of Metabolism

Urea cycle disorders (UCD)

Urea cycle disorders (UCD)
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 (NAGS) deficiency
Ornithine transcarbamylase (OTC) deficiency

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

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 health care provider 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 of Urea cycle disorders
The main goal of treatment of UCDs is to avoid hyperammonemia in order to prevent neurological consequences. Chronic treatment consists of reduction of dietary protein along with pharmaceuticals and supplementation of essential amino acids, vitamins, trace elements. Additional treatment options for some patients are dialysis or liver transplantation.

References:

National Library of Medicine (NLM)
Häberle J, McCandless S. Orphan drugs in development for UCDs, Orphan Drugs Research and Reviews 2014