Argininemia: A Rare Disorder of Amino Acid Metabolism

Argininemia: An Inherited Metabolic Disorder

Overview

Argininemia is a rare, inherited metabolic disorder characterized by a deficiency in argininosuccinate synthetase (ASS), an enzyme involved in the urea cycle. The urea cycle is responsible for eliminating excess nitrogen from the body in the form of urea. A deficiency in ASS leads to a buildup of ammonia, a toxic substance, in the bloodstream.

Types of Argininemia

There are two main types of argininemia:

1. Type I Argininemia (Classical Argininemia): This is the most severe form and is caused by mutations in the ASS1 gene, which encodes for the ASS enzyme. It typically presents in infancy and can be life-threatening if untreated.

2. Type II Argininemia (Argininemia-Hyperornithinemia-Homocitrullinuria Syndrome): This milder form is caused by mutations in the OTC gene, which encodes for the ornithine transcarbamoylase (OTC) enzyme, another enzyme involved in the urea cycle. It typically presents later in childhood or adolescence.

Symptoms

The symptoms of argininemia vary depending on the severity of the disorder and the type.

Type I Argininemia:

• Vomiting
• Diarrhea
• Poor feeding
• Lethargy
• Tremors
• Seizures
• Coma
• Death

Type II Argininemia:

• Growth retardation
• Intellectual disability
• Behavioral problems
• Movement disorders
• Liver disease
• Seizures

Diagnosis

Argininemia is diagnosed through blood and urine tests that measure levels of ammonia, amino acids (arginine, ornithine, and citrulline), and other metabolites. Genetic testing can also confirm the diagnosis by identifying mutations in the ASS1 or OTC genes.

Treatment

Treatment for argininemia focuses on:

1. Ammonia Removal:

• Dietary restrictions to reduce protein intake
• Medications to promote ammonia removal (hemodialysis, peritoneal dialysis)

2. Arginine Supplementation:

• To correct the deficiency and promote urea cycle function

3. Other Medications:

• Anticonvulsants for seizures
• Growth hormone for growth retardation
• Liver transplantation in severe cases

Prognosis

With early diagnosis and treatment, the prognosis for argininemia has improved significantly. However, complications can still occur, and lifelong monitoring is necessary.

Type I Argininemia:

• Untreated, it is fatal within the first few months of life.
• With treatment, survival rates are around 75%.

Type II Argininemia:

• Less severe, with a better prognosis.
• However, intellectual disability and behavioral problems can persist despite treatment.

Genetics

Argininemia is inherited in an autosomal recessive manner. This means that both parents must carry a copy of the mutated gene for a child to inherit the disorder.

Epidemiology

Argininemia is a rare condition. Type I argininemia occurs in approximately 1 in 70,000 to 100,000 newborns. Type II argininemia is even rarer, occurring in approximately 1 in 100,000 newborns.

Screening

Routine newborn screening for argininemia is not widely available. However, it is recommended for families with a history of the disorder.

Conclusion

Argininemia is a rare but serious metabolic disorder that requires early diagnosis and treatment. Advances in medical management have improved the prognosis for individuals with argininemia, but ongoing monitoring and care are essential to ensure optimal health outcomes.