Published: 18 Jun 2025

ICD9: 270.6      ICD10: E72.20      ICD11: 5C50.AZ

A urea cycle disorder (UCD) is a genetic condition that causes ammonia to build up in the blood.
Here's a breakdown:

What is the Urea Cycle?

The urea cycle is a series of biochemical reactions that occur in the liver.
Its primary purpose is to remove ammonia, a toxic waste product of protein metabolism, from the body.
Ammonia is converted into urea, a less toxic substance that can be excreted in urine.

What Happens in a UCD?

In UCDs, one of the enzymes in the urea cycle is either deficient or completely missing.
This deficiency prevents the cycle from functioning correctly, leading to a buildup of ammonia in the blood (hyperammonemia).
Ammonia is toxic, especially to the brain, and can cause irreversible brain damage, coma, and even death if not treated promptly.

Causes

UCDs are caused by genetic mutations (changes) in genes that provide instructions for making the enzymes of the urea cycle.
Most UCDs are inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for the child to be affected. There is also one X-linked urea cycle disorder.

Types of UCDs

There are several different types of UCDs, depending on which enzyme is affected:

Ornithine transcarbamylase deficiency (OTC): Most common UCD. X-linked.
Carbamoyl phosphate synthetase I deficiency (CPS1):
Argininosuccinate synthetase deficiency (ASS1), also known as citrullinemia type I:
Argininosuccinate lyase deficiency (ASL):
Arginase deficiency (ARG1):
N-acetylglutamate synthase deficiency (NAGS): Rarest UCD.

Symptoms

Symptoms vary depending on the severity of the deficiency and the age of onset, but may include:

In newborns:
Lethargy
Poor feeding
Vomiting
Irritability
Rapid breathing
Seizures
Coma
In older children and adults:
Confusion
Headaches
Behavioral changes
Slurred speech
Ataxia (lack of coordination)
Avoidance of high-protein foods
Cyclic vomiting
Seizures
Coma

Diagnosis

Blood tests: Elevated ammonia levels are a key indicator. Other tests to check amino acid levels (citrulline, arginine, etc.) are important.
Urine tests:
Genetic testing: To identify the specific gene mutation.
Enzyme assays: (Less commonly done now with readily available genetic testing) Measure the activity of the urea cycle enzymes.

Treatment

Treatment focuses on lowering ammonia levels and preventing future episodes of hyperammonemia. It is a lifelong undertaking. Treatment options include:

Dietary management:
Restricting protein intake.
Providing special formulas and foods low in protein but high in calories.
Medications:
Ammonia scavengers: Drugs like sodium benzoate and sodium phenylbutyrate help the body get rid of ammonia through alternative pathways.
Arginine or citrulline supplementation: Some UCDs benefit from supplementation.
Hemodialysis or hemofiltration: In severe cases, these procedures can rapidly remove ammonia from the blood.
Liver transplantation: A liver transplant can cure UCDs by providing a functional urea cycle. This is considered a definitive treatment for some, but carries its own risks and requires lifelong immunosuppression.

Prognosis

The prognosis for individuals with UCDs depends on the severity of the deficiency, the age of diagnosis, and how well the condition is managed. Early diagnosis and treatment are crucial to minimize brain damage and improve outcomes. Lifelong adherence to treatment is necessary.

Importance of Newborn Screening

Many states include UCDs in their newborn screening programs, which allows for early diagnosis and intervention, significantly improving outcomes. This is typically done through a blood test (heel prick) shortly after birth.

It is important to consult with a medical professional for accurate diagnosis and treatment of Urea Cycle Disorders. This is a complex condition, and management should be individualized.