Argininemia

Argininemia, also known as arginase deficiency or hyperargininemia, is a rare autosomal recessive urea cycle disorder caused by deficiency of the enzyme arginase 1 (ARG1), which catalyzes the final step of the urea cycle — the conversion of arginine to ornithine and urea. This deficiency leads to the accumulation of arginine and its metabolites (including guanidino compounds) in the blood and cerebrospinal fluid. Unlike other urea cycle disorders, argininemia typically does not present with severe neonatal hyperammonemic crises, though mild to moderate hyperammonemia can occur. The disease primarily affects the central nervous system and manifests during early childhood, usually between ages 2 and 4 years. Key clinical features include progressive spastic diplegia (particularly affecting the lower limbs), intellectual disability, seizures, growth retardation, and episodic hyperammonemia. The spasticity is progressive and can lead to loss of ambulation. Affected individuals may also develop microcephaly, irritability, and feeding difficulties. The guanidino compounds that accumulate are thought to be neurotoxic and contribute significantly to the neurological manifestations. Treatment of argininemia involves dietary management with restriction of protein and arginine intake, supplemented with essential amino acids. Nitrogen-scavenging medications such as sodium benzoate and sodium phenylbutyrate may be used to help control hyperammonemia. Liver transplantation has been performed in some cases and can normalize arginase activity and reduce arginine levels, though it may not fully reverse established neurological damage. Early diagnosis through newborn screening programs, which can detect elevated arginine levels, is critical for initiating treatment before irreversible neurological injury occurs.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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