Urea Cycle Disorders

Urea cycle disorders (UCDs) are a group of inherited diseases that affect a child’s ability to process protein waste products. The urea cycle acts like a filter in your body, helping to get rid of harmful substances and keep the beneficial ones moving where the need arises

Here’s how it works: Your liver produces a substance called urea, which is essential for removing waste from your body. When you eat protein, your body breaks it down into smaller units called amino acids. These amino acids are crucial for building muscles, transporting nutrients, and maintaining organ function. However, during this process, it produces waste products like ammonia, which can be toxic.

To deal with this toxicity, special proteins called enzymes step in. They convert the harmful ammonia into urea, along with certain amino acids like arginine, ornithine, and citrulline. This urea then travels through your bloodstream to your kidneys, where one can excrete it through urine.

But sometimes, things can go awry. Urea cycle disorder is a group of genetic conditions where this process doesn’t work properly due to missing or malfunctioning proteins or enzymes. This leads to a buildup of ammonia in the blood, which can be harmful to the brain and organs.

Types of urea cycle disorders

There are eight types of urea cycle disorders, each caused by a deficiency in a specific enzyme or protein involved in the urea cycle.

These urea cycle disorders are named after the specific enzyme or protein that’s deficient. They include:

1. N-acetylglutamate synthase (NAGS) deficiency.
2. Carbamoylphosphate synthetase I (CPS1) deficiency.
3. Ornithine transcarbamylase (OTC) deficiency.
4. Argininosuccinate synthase 1 (ASS1) deficiency or citrullinemia type I.
5. Citrin deficiency, or Citrullinemia type II,.
6. Argininosuccinic lyase (ASL) deficiency.
7. Arginase (ARG) deficiency.
8. Ornithine translocase deficiency.

Healthcare providers often screen newborns shortly after birth for these disorders, although they can manifest at any age. Symptoms can vary widely and may include vomiting, lethargy, irritability, seizures, and even coma if left untreated.

Who Gets Urea Cycle Disorders (UCDs)

UCDs are rare, affecting about 1 in 35,000 newborns. There are eight different types, each named after the missing enzyme. These disorders are usually passed down from parents through genes.

Causes of Urea Cycle Disorders (UCDs)

Urea cycle disorder stems from genetic mutations that affect specific genes responsible for producing essential proteins and enzymes crucial for moving urea through your body. A distinct genetic mutation links each type of urea cycle disorder:

• N-acetylglutamate synthase deficiency results from a mutation in the NAGS gene.
• A mutation in the CPS1 gene causes carbamoylphosphate synthetase I deficiency.
• Ornithine transcarbamylase deficiency is associated with mutations in the OTC gene.
• Argininosuccinate synthase 1 deficiency is due to mutations in the ASS1 gene.
• Citrin deficiency arises from mutations in the SLC25A13 gene.
• Mutations in the ASL gene cause argininosuccinic lyase deficiency.
• Arginase deficiency results from mutations in the ARG gene.
• Mutations in the SLC25A15 gene cause ornithine translocase deficiency.

When these genes undergo mutations, the production of necessary proteins and enzymes becomes insufficient, impairing the body’s ability to remove toxic ammonia effectively. As a result, ammonia accumulates in the bloodstream, leading to various symptoms characteristic of urea cycle disorder.

Symptoms of Urea cycle disorders (UCDs)

Symptoms can vary depending on the severity of the enzyme deficiency.

• Newborns with complete UCDs: Show symptoms within days of birth, including fussiness, sleepiness, poor feeding, vomiting, low body temperature, breathing problems, seizures, and coma.
• Children with partial UCDs may not show symptoms for months or even years. Symptoms can include food aversion, especially to protein-rich foods, loss of appetite, nausea, vomiting, behavioral problems, and mental issues.

Diagnosis of Urea cycle disorders (UCDs)

The diagnosis of urea cycle disorder typically involves a thorough physical examination, symptom review, and comprehensive medical history assessment by a healthcare provider. Additionally, diagnostic tests may include the following:

• Amino acid profile analysis: This test measures the levels of amino acids processed by your body, often using blood or urine samples.
• Liver biopsy: A small sample of liver tissue is examined under a microscope to identify any enzyme abnormalities associated with the disorder.
• Genetic testing: Blood samples are analyzed to detect genetic mutations responsible for the symptoms.

Treatment of UCDs

UCDs are life-threatening and require immediate treatment. This typically involves:

• Dialysis: removes ammonia from the blood.
• Specialized diet: low-protein, high-calorie food and amino acid supplements.
• Medications: Help remove excess nitrogen.

Long-term management of UCDs

• Strict diet: low protein, high- calories to prevent ammonia buildup.
• Medications: To continuously remove extra nitrogen.
• Supplements: To ensure proper nutrition.
• Hydration: Drinking plenty of fluids is crucial.
• Liver transplant: In some cases, a liver transplant can potentially cure the condition.

Living with UCDs:

There’s no cure for UCDs, but with early diagnosis, strict adherence to treatment plans, and careful management during stressful periods, children with UCDs can lead normal, healthy lives.