What happens if the urea cycle is defective?

A defective urea cycle causes ammonia to build up in the blood. Ammonia is toxic and mainly damages the brain and nervous system. Symptoms can range from mild problems like learning difficulties to life-threatening issues such as seizures, coma, or even death. 

In newborns, warning signs often appear within the first few days of life and may include poor feeding, unusual sleepiness, or vomiting. Detecting high ammonia levels early is critical to start treatment and protect the brain from permanent damage.

How the Urea Cycle Normally Works

1. Protein Breakdown: When you eat protein, it is broken down into amino acids.
2. Ammonia Production: Any leftover amino acids produce ammonia as waste.
3. Liver’s Job: The liver uses special enzymes to turn harmful ammonia into urea.
4. Excretion: Urea is safely removed from the body through urine.

What Happens When the Cycle Is Defective

• Ammonia Build-Up: The body cannot properly convert ammonia into urea.
• Hyperammonemia: This causes dangerously high levels of ammonia in the blood.

Symptoms and Signs

In Newborns:

• Healthy at birth, then poor feeding, vomiting, or excessive sleepiness.
• May become irritable, difficult to wake, or show lethargy.
• If ammonia keeps rising: seizures, confusion, coma, and risk of death.

In Older Children and Adults:

• Confusion, mood or behavior changes, or dislike of high-protein foods.
• Sometimes milder problems, such as slow development or psychiatric symptoms.

Why This Is Dangerous

• Ammonia Toxicity: Ammonia directly harms brain cells.
• Brain Swelling: High ammonia can cause swelling in the brain (cerebral edema).
• Severe Outcomes: This may raise pressure inside the skull, leading to brain damage, coma, or death.