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Understanding Urea Cycle Disorders: Causes, Symptoms, Diagnosis, and Treatment

Urea cycle disorders (UCDs) are a group of inherited diseases that affect the body's ability to remove waste products from protein digestion. When a child with a UCD eats protein, their body breaks it down into amino acids and uses what it needs. The remaining waste products are typically broken down further and removed from the body through a process called the urea cycle. However, in children with UCDs, the liver cannot produce one of the essential enzymes required for this process, leading to a buildup of toxic ammonia in the blood.

Who Gets Urea Cycle Disorders?

UCDs affect approximately 1 in 35,000 newborns. There are eight types of UCDs, each named after the missing enzyme in the urea cycle. Parents pass these diseases down to their children through defective genes. In most cases, a child must inherit a defective gene from both parents to develop a UCD. However, one type of UCD called ornithine transcarbamylase (OTC) deficiency is a sex-linked disorder, primarily affecting males who inherit the defective gene from their mothers.

Symptoms of Urea Cycle Disorders

UCDs are classified into two groups: complete and partial. In complete UCDs, the baby has a severe or total lack of the enzyme, and symptoms appear within the first few days of life. These symptoms may include:

  • Fussiness

  • Sleepiness or sluggishness

  • Feeding difficulties

  • Vomiting

  • Low body temperature

  • Posture problems

  • Seizures

  • Breathing issues

  • Coma

In partial UCDs, the baby can produce some of the enzyme, but not enough. Symptoms may not appear for months or even years and are usually less severe. These symptoms can be triggered by illness, injury, stress, or rapid weight loss and may include:

  • Avoidance of high-protein foods or dislike of meat

  • Loss of appetite

  • Nausea or vomiting

  • Behavioral problems, such as hyperactivity

  • Mental issues, including confusion, delusions, hallucinations, or psychosis

Diagnosing Urea Cycle Disorders

Most newborns in the United States are tested for two types of UCDs: ASS1 and ASL deficiencies. Many states also test for arginase and citrin deficiencies, while a few states test for OTC and CPS1 deficiencies. If a baby develops symptoms after going home, doctors will perform a physical exam, review family history, and conduct tests to look for ammonia in the blood and amino acids in the blood and urine. A liver biopsy may be performed to test for enzymes, and genetic tests can confirm the diagnosis.

Treating Urea Cycle Disorders

UCDs are life-threatening, and immediate treatment is crucial. A team of health professionals will provide care, starting with three simultaneous treatments:

  1. Dialysis to remove ammonia from the blood

  2. Feeding supplements containing sugars, fats, and amino acids

  3. Medications to remove excess nitrogen

Long-term treatment focuses on managing UCD symptoms and includes:

  • A low-protein, high-calorie diet

  • Medications to remove nitrogen

  • Amino acid supplements

  • Drinking plenty of water

In some cases, a liver transplant can reverse the symptoms of a UCD.

Outlook for Children with Urea Cycle Disorders

There is no cure for UCDs, and a child's long-term health depends on the specific type of UCD, its severity, how early it was diagnosed, and adherence to the treatment plan. Repeated brain swelling due to not following the special diet or experiencing frequent stress-induced symptoms can lead to irreversible brain damage. However, with early diagnosis and strict adherence to the treatment plan, children with UCDs can live normal lives.

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