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Arginase deficiency
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Arginase deficiency

Arginase deficiency is an inherited urea cycle disorder that leads to the toxic accumulation of ammonia and arginine in the blood, primarily affecting the nervous system.

Overview

Arginase deficiency is an inherited disorder that causes the amino acid arginine (a building block of proteins) and ammonia to accumulate gradually in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

Symptoms

Arginase deficiency usually becomes evident by about the age of 3. Symptoms may include:

  • Stiffness, especially in the legs, caused by abnormal tensing of the muscles (spasticity)
  • Slower than normal growth
  • Developmental delays and eventual loss of developmental milestones
  • Intellectual disabilities
  • Seizures
  • Tremors
  • Difficulty with balance and coordination (ataxia)

Occasionally, high-protein meals or stress caused by illness or periods without food (fasting) may cause ammonia to accumulate more quickly in the blood. This rapid increase in ammonia may lead to episodes of irritability, refusal to eat, and vomiting. In some affected individuals, the signs and symptoms may be less severe and may not appear until later in life.

Frequency

Arginase deficiency is a very rare disorder; it has been estimated to occur once in every 300,000 to 1,000,000 individuals.

Causes

Arginase deficiency is caused by variants (mutations) in the ARG1 gene, which provides instructions for making an enzyme called arginase. This condition belongs to a class of genetic diseases called urea cycle disorders.

The urea cycle is a sequence of reactions that processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the body. The arginase enzyme facilitates the final step of this cycle. In people with arginase deficiency, the enzyme is damaged or missing, preventing the proper breakdown of arginine. Consequently, urea cannot be produced normally, and excess nitrogen accumulates in the blood as ammonia.

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell must have a variant to cause the disorder. Parents of an individual with an autosomal recessive condition each carry one copy of the altered gene but typically do not show signs or symptoms of the condition.

Other Names

  • ARG1 deficiency
  • Arginase deficiency disease
  • Argininemia
  • Hyperargininemia

Frequently Asked Questions

Early signs of an acute crisis include sudden irritability, lethargy, refusal to eat, and vomiting. These symptoms often appear after a period of stress, such as an illness, fasting, or a high-protein meal. It is critical to seek immediate medical attention if these symptoms occur, as rapid intervention with dialysis or specific medications is required to lower ammonia levels. Parents should be educated to monitor for these behavioral and physical changes closely, especially during times of physiological stress, to prevent permanent neurological damage.
The ARG1 gene provides instructions for making the enzyme arginase, which is responsible for breaking down the amino acid arginine into urea and ornithine. When this enzyme is deficient, arginine accumulates in the blood, and because the urea cycle is disrupted, ammonia also builds up. Ammonia is highly toxic to the brain, leading to the neurological symptoms such as spasticity, seizures, and developmental delays. The specific accumulation of arginine also contributes to cellular damage, particularly in the nervous system, which explains the unique clinical profile of this disorder compared to other urea cycle defects.
Management requires a low-protein diet to limit the intake of arginine and reduce ammonia production. This involves restricting natural protein sources like meat, dairy, and eggs, and often supplementing with special medical formulas that provide essential amino acids while excluding arginine. The strictness of the diet is individualized based on blood levels of arginine and ammonia, but it must be maintained consistently for life. Even small deviations can lead to toxic accumulation of ammonia, so careful monitoring by a metabolic dietitian is essential to ensure adequate nutrition without triggering metabolic crises.
Life expectancy varies significantly among individuals, with some living into adulthood while others face severe complications. The primary long-term concern is progressive neurological damage due to repeated or chronic exposure to high ammonia levels. This can result in spasticity, intellectual disability, and loss of developmental milestones. Early and consistent management of ammonia levels is crucial to minimize this damage, but some degree of neurological impairment is common in many affected individuals, requiring ongoing physical and occupational therapy.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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