Published: 18 Jun 2025

ICD9: 270.6      ICD10: E72.21      ICD11: 5C50.A2

Argininemia, also known as Arginase Deficiency, is a rare genetic disorder caused by a deficiency of the enzyme arginase.
This enzyme plays a critical role in the urea cycle, a biochemical pathway in the liver responsible for removing ammonia, a toxic waste product, from the body.

Here's a breakdown of what you need to know:

Key Aspects:

Cause: A deficiency in the enzyme arginase, which is encoded by the *ARG1* gene. This deficiency is usually inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for their child to be affected.
Urea Cycle Disruption: Arginase is the final enzyme in the urea cycle. It converts arginine into urea and ornithine. Without enough arginase, arginine accumulates in the blood and bodily fluids, and the body struggles to get rid of excess nitrogen in the form of ammonia.
Ammonia Toxicity (Hyperammonemia): While the degree of hyperammonemia (high ammonia levels in the blood) is usually milder compared to other urea cycle disorders, it can still lead to neurological problems. The accumulation of arginine and other urea cycle intermediates also contributes to the symptoms.
Arginine Accumulation: Elevated levels of arginine in the blood can interfere with other metabolic pathways. The buildup of arginine is a key diagnostic marker.
Symptoms: The symptoms and their severity vary, but common signs and symptoms include:
Developmental Delay: Often one of the first signs.
Progressive Spasticity (Muscle Stiffness): Primarily affecting the legs, leading to difficulty walking and coordination. This is a hallmark symptom and often distinguishes it from other urea cycle disorders.
Seizures: Can occur in some individuals.
Intellectual Disability: Ranges in severity.
Growth Problems: May experience slowed growth.
Hyperactivity and Irritability: Common behavioral issues.
Tremors: Involuntary shaking.
Feeding Difficulties: Especially in infancy.
Liver problems: Less common but possible.
Diagnosis:
Newborn Screening: In some regions, argininemia may be detected through newborn screening programs that test blood samples for elevated arginine levels.
Blood Tests: Measuring arginine and ammonia levels in the blood. Genetic testing can confirm the diagnosis by identifying mutations in the *ARG1* gene.
Urine Tests: Measuring orotic acid and other urea cycle intermediates can provide clues.
Treatment: Management focuses on reducing ammonia levels and managing the symptoms. This usually involves:
Dietary Management: A low-protein diet is crucial to reduce the amount of nitrogen the body has to process. Careful monitoring by a metabolic dietician is essential. Arginine supplementation should be avoided.
Medications:
Ammonia-Lowering Drugs: Medications like sodium benzoate and sodium phenylacetate (e.g., Buphenyl or Ammonul) help the body eliminate nitrogen through alternative pathways.
L-Arginine-Free Amino Acid Formulas: Specialized formulas can help ensure proper nutrition without adding more arginine.
Physical Therapy: To manage spasticity and improve mobility.
Occupational Therapy: To help with fine motor skills and activities of daily living.
Monitoring: Regular monitoring of arginine and ammonia levels is vital to adjust treatment as needed.
Liver Transplant: In severe cases, a liver transplant may be considered. This can restore the function of the urea cycle and eliminate the need for lifelong dietary restrictions and medications.
Prognosis: The prognosis varies depending on the severity of the condition and the effectiveness of treatment. Early diagnosis and consistent adherence to the treatment plan can improve the outcome and minimize long-term complications.

In summary, Argininemia is a genetic disorder that disrupts the urea cycle, leading to a buildup of arginine and ammonia in the blood. This can cause neurological problems, developmental delays, and spasticity. Treatment focuses on managing ammonia levels through dietary restrictions and medications, and addressing symptoms with therapies.

If you suspect someone might have argininemia, it is crucial to consult with a medical professional, especially a metabolic specialist. They can provide accurate diagnosis, genetic counseling, and appropriate management strategies.