Two Japanese siblings with arginase-1 deficiency identified using a novel frameshift mutation of ARG1 (p.Lys41Thrfs*2)

We described two Japanese siblings with arginase-1 (ARG1) deficiency. A 10-year-old girl (the proband and elder sister) was referred to our hospital complaining about her short stature. We diagnosed her with ARG1 deficiency, possibly with elevated levels of blood ammonia and plasma arginine. Her younger sister was found to have spastic paraparesis in her lower extremities and short stature at the age of 4 years. The younger sister also had high levels of plasma arginine, instead of normal levels of blood ammonia. Interestingly, they also prefer to avoid protein-rich foods such as meat, soybeans, cow milk, and dairy products. Genetic testing identified compound heterozygous mutations (c.121_122insCTT [p.Lys41Thrfs*2] and c.298G>A [p.Asp100Asn]) in the ARG1 gene. The ARG1 mutation of p.Lys41Thrfs*2 is a novel pathogenic mutation according to open databases and literature.