What Are Urea Cycle Disorders?

Urea cycle disorders (UCDs) are a group of diseases. They make it hard for your child’s body to remove waste products as they digests proteins. They are inherited diseases -- you pass them down to your child.

In most cases, you can manage them with diet and medications.

When your baby eats protein, their body breaks it down into amino acids and uses what they need. What they don’t need is further broken down into waste products that their body removes.

This happens in a process called the urea cycle. Your baby’s liver makes things called enzymes that turn waste nitrogen into urea. The urea leaves their body in their urine.

If your child has a urea cycle disorder, their liver can’t make one of the enzymes the cycle needs. When their body can’t remove nitrogen, ammonia forms and collects in their blood. It’s toxic and can cause brain damage or put them in a coma. It can even be fatal if you don’t treat it quickly.

Who Gets Them?

UCDs affect about 1 in 35,000 newborns.

There are eight types. They’re named after what’s missing from the urea cycle. You’ll also hear doctors call them by their initials:

  • ARG1 deficiency -- Arginase
  • ASL deficiency -- Argininosuccinate lyase
  • ASS1 deficiency -- Argininosuccinate synthase 1
  • Citrin deficiency -- Citrin
  • CPSI deficiency -- Carbamoyl phosphate synthetase I
  • NAGS deficiency -- N-acetylglutamate synthase
  • ORNT1 deficiency -- Ornithine translocase
  • OTC deficiency -- Ornithine transcarbamylase

Parents pass these diseases down to their children through defective genes. We all inherit two copies of our genes, one from each parent. With most UCDs, you must get a defective gene from both parents to get the disease. The genes tell your child’s body how to break down protein.

One UCD, called ornithine transcarbamylase (OTC) deficiency, is what doctors call a sex-linked disorder. Mothers carry the gene on their X chromosome, and they mostly pass it to their sons.

Symptoms

UCDs fall into two groups:

Complete UCD: This means your baby has a severe or total lack of the enzyme. You’ll notice symptoms in the first couple of days:

  • Fussy
  • Sleepy or sluggish
  • Can’t feed
  • Vomits
  • Low body temperature
  • Problems with posture
  • Seizures
  • Fast breathing that becomes slow
  • Coma

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Partial UCD: Your baby can make some of the enzyme, but not as much as they need. You may not spot symptoms for months or even years.

A buildup of ammonia (you may hear the doctor call it hyperammonemia) can happen from illness, injury, stress, or quick weight loss.

Symptoms are usually less severe than in babies with complete UCD. They include:

Diagnosis

Most newborns in the U.S. are tested for ASS1 and ASL, but how well the tests work is different in each state. Many states test for arginase and citrin deficiencies. A handful also test for OTC and CPS1 deficiencies.

If your baby starts to show symptoms after you get home, the doctor will do a physical exam. They’ll ask about your family history and do tests. They’ll look for ammonia in your child’s blood and amino acid in their blood and urine. The doctor can take a tiny piece of their liver through a process called biopsy. They’ll test it for enzymes. Genetic tests will usually confirm the diagnosis.

Treatment

UCDs are life-threatening. Don’t wait to get treatment.

A team of health professionals will care for your child. They will first do these three treatments at the same time:

  • Dialysis to remove ammonia from their blood
  • Feeding them supplements of sugars, fats, and amino acids
  • Medicines to remove extra nitrogen

Long-term treatment can manage UCD symptoms. Your child will need frequent blood tests throughout their life to check ammonia levels. Stresses on their body -- like illness, injury, or surgery -- can cause their levels to rise. During those times, you’ll need to give them extra calories so their body has plenty of fuel.

Long-term treatment will include:

  • A low protein, high-calorie diet
  • Medications to remove nitrogen
  • Supplements of amino acids
  • Drinking plenty of water

A liver transplant can reverse the symptoms of a urea cycle disorder.

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Outlook

There’s no cure for UCDs. Your child’s long-term health depends on which UCD they have, how severe it is, how early it was diagnosed, and how closely you follow the treatment plan.

If your child doesn’t follow the special diet or they have frequent stress-induced symptoms, repeated brain swelling can lead to irreversible brain damage. If they’re diagnosed early and follows their diet, they can live a normal life.

WebMD Medical Reference Reviewed by Dan Brennan, MD on October 30, 2019

Sources

SOURCES:

National Organization for Rare Disorders: “Ornithine Transcarbamylase Deficiency,” “Urea Cycle Disorders (UCD).”

Cincinnati Children’s: “Urea Cycle Disorder (UCD).”

Gene Reviews: “Urea Cycle Disorders Overview.”

Summar, M. Molecular Genetics and Metabolism, September 2013.

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