Carbamoyl phosphate synthetase deficiency

A rare genetic disorder affecting the urea cycle

Carbamoyl phosphate synthetase deficiency
[[File:|250px|]]
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Hyperammonemia, lethargy, vomiting, seizures
Complications	N/A
Onset	Neonatal
Duration	Lifelong
Types	N/A
Causes	Mutations in the CPS1 gene
Risks	N/A
Diagnosis	Genetic testing, blood ammonia levels
Differential diagnosis	N/A
Prevention	N/A
Treatment	Dietary management, medications
Medication	N/A
Prognosis	Variable
Frequency	N/A
Deaths	N/A

Carbamoyl phosphate synthetase deficiency is a rare genetic disorder that affects the urea cycle, a series of biochemical reactions that occur in the liver to remove ammonia from the bloodstream. This condition is caused by mutations in the CPS1 gene, which encodes the enzyme carbamoyl phosphate synthetase 1. This enzyme is crucial for the first step of the urea cycle, where it catalyzes the synthesis of carbamoyl phosphate from ammonia and bicarbonate.

Pathophysiology

Carbamoyl phosphate synthetase 1 (CPS1) is an enzyme located in the mitochondria of liver cells. It plays a critical role in the urea cycle by converting ammonia, a toxic byproduct of protein metabolism, into carbamoyl phosphate. This compound is then used to produce citrulline, which eventually leads to the formation of urea, a less toxic compound that is excreted in the urine.

In individuals with carbamoyl phosphate synthetase deficiency, the CPS1 enzyme is either absent or nonfunctional due to mutations in the CPS1 gene. As a result, ammonia accumulates in the blood, leading to a condition known as hyperammonemia. High levels of ammonia are toxic to the brain and can cause neurological symptoms and damage.

Clinical Presentation

The symptoms of carbamoyl phosphate synthetase deficiency typically appear in the neonatal period, often within the first few days of life. Common symptoms include:

• Lethargy
• Poor feeding
• Vomiting
• Hypothermia
• Seizures
• Coma

If left untreated, the condition can lead to severe neurological impairment or death.

Diagnosis

Diagnosis of carbamoyl phosphate synthetase deficiency is based on clinical presentation, laboratory findings, and genetic testing. Key diagnostic tests include:

• Measurement of blood ammonia levels, which are typically elevated.
• Analysis of plasma amino acids, which may show low levels of citrulline.
• Genetic testing to identify mutations in the CPS1 gene.

Treatment

Management of carbamoyl phosphate synthetase deficiency involves reducing ammonia levels in the blood and preventing hyperammonemic crises. Treatment strategies include:

• Dietary management: A low-protein diet to reduce ammonia production.
• Medications: Use of ammonia-scavenging drugs such as sodium phenylbutyrate or sodium benzoate.
• Liver transplantation: In severe cases, liver transplantation may be considered as it can provide a source of functional CPS1 enzyme.

Prognosis

The prognosis for individuals with carbamoyl phosphate synthetase deficiency varies depending on the severity of the enzyme deficiency and the effectiveness of treatment. Early diagnosis and management are crucial for improving outcomes and preventing neurological damage.

Also see

• Urea cycle disorder
• Ornithine transcarbamylase deficiency
• Argininosuccinate lyase deficiency
• Hyperammonemia