Argininemia presenting with progressive spastic diplegia

Argininemia is caused by a deficiency of arginase 1, which catalyzes the final step in the urea cycle, i.e., the cytosolic hydrolysis of arginine to ornithine and urea. In contrast to other urea cycle disorders, hyperammonemic encephalopathy is rarely observed in patients with argininemia. Rather, most exhibit an insidious onset and progression of neurologic manifestations, including spastic diplegia. We describe the first Korean patient with argininemia, manifesting as slowly progressive spastic diplegia. Our patient carries c.[32T>C]+[913G>A] (p.[Ile11Thr]+[Gly305Arg]) mutations in the ARG1 gene. The latter mutation was not previously reported. Although argininemia is a very rare disease, it is recognized as a pan-ethnic disorder. We conclude that argininemia should be considered more frequently in the differential diagnosis of a patient with slowly progressive neurologic manifestations, especially progressive spastic diplegia, even in a population where argininemia was previously unknown.