Arginase Deficiency
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The arginase gene is located on chromosome 6q23 composed of 8 exons encoding a protein of 322 amino acids. The functional enzyme exists as a homotrimer. There are in fact two distinct arginase genes identified as ARG1 and ARG2. ARG1 is the liver enzyme contributing 98% of the arginase activity in that organ. ARG2 encodes a mitochondrial arginase found predominately in the kidneys. Mutations in ARG1 give rise to hyperargininemia also known as arginase deficiency (AD). Mutations in arginase are rare and the frequency of AD is approximately 1 per 363,000 live births.
The major symptoms of AD are all progressive and include psychomotor retardation, spastic tetraplegia where the lower limbs are more affected than the upper, hyperactivity, growth failure and seizures. Because arginase catalyzes the last reaction of the urea cycle, hyperammonemia is not as severe as in other neonatal UCDs (3-4 times normal as opposed to 6 times normal in say OTCD). The most prominent laboratory findings in AD are mild hyperammonemia, hyperargininemia, hyperaminoaciduria (arginine, lysine, ornithine and cystine) and orotic aciduria.
AD patients are treated in much the same ways as for other neonatal UCDs in that protein intake must me highly regulated and the hyperammonemia must be controlled. Hemodialysis is the only effective means to rapidly lower serum ammonia levels in these patients. Acute episodes of hyperammonemia can be treated with intravenous administration of Ammunol® and with oral Buphenyl® for chronic adjunctive therapy of hyperammonemia.
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Michael W. King, Ph.D / IU School of Medicine / miking at iupui.edu