Citrullinuria

Citrullinuria Citrullinuria is a rare metabolic disorder characterized by the excessive excretion of citrulline in the urine. It is a condition that arises due to a defect in the urea cycle, which is responsible for removing ammonia from the bloodstream. This article will explore the causes, symptoms, diagnosis, and treatment of citrullinuria, as well as its genetic basis and implications for affected individuals.

Causes

Citrullinuria is primarily caused by a deficiency in the enzyme argininosuccinate synthetase, which is crucial for the conversion of citrulline to argininosuccinate in the urea cycle. This enzyme deficiency leads to the accumulation of citrulline in the blood and its subsequent excretion in the urine.

Genetic Basis

Citrullinuria is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the defective gene, one from each parent, to manifest the disorder. The gene responsible for this condition is located on chromosome 9 and is known as ASS1.

Symptoms

The symptoms of citrullinuria can vary widely among affected individuals. Common symptoms include:

• Lethargy
• Poor feeding
• Vomiting
• Developmental delay
• Seizures

In severe cases, the accumulation of ammonia in the blood can lead to hyperammonemia, which is a life-threatening condition.

Diagnosis

Diagnosis of citrullinuria typically involves a combination of clinical evaluation, biochemical tests, and genetic testing. Key diagnostic tests include:

• Plasma amino acid analysis to detect elevated levels of citrulline.
• Urine organic acid analysis.
• Genetic testing to identify mutations in the ASS1 gene.

Treatment

Management of citrullinuria focuses on reducing ammonia levels in the blood and preventing hyperammonemia. Treatment strategies may include:

• Dietary modifications to limit protein intake.
• Medications such as sodium benzoate or sodium phenylbutyrate to help remove excess ammonia.
• In severe cases, liver transplantation may be considered.

Prognosis

The prognosis for individuals with citrullinuria varies depending on the severity of the enzyme deficiency and the effectiveness of treatment. Early diagnosis and intervention are crucial for improving outcomes and preventing complications.

Research and Future Directions

Ongoing research into citrullinuria aims to improve diagnostic methods, develop more effective treatments, and explore potential gene therapy options. Advances in genetic research may offer new insights into the management of this rare disorder.

See Also

• Urea cycle disorder
• Hyperammonemia
• Metabolic disorder

External Links

• National Organization for Rare Disorders
• Genetic and Rare Diseases Information Center

NIH genetic and rare disease info

• NIH info on Citrullinuria

Citrullinuria is a rare disease.