Clinical, biochemical, and genetic features of non-classical 21-hydroxylase deficiency in Japanese children.

Non-classical 21-hydroxylase deficiency (NC21-OHD) is a mild form of 21-hydroxylase deficiency lacking apparent symptoms of androgen excess at birth. Most NC21-OHD cases are diagnosed after the onset of puberty, while a substantial number of patients are not diagnosed during childhood. Previous studies have reported ethnic differences in the prevalence of NC21-OHD. To date, the clinical features of NC21-OHD in Japanese children have not been systemically reported. Thus, we performed 3 independent analyses: retrospective analyses of newborn screening in 2 major Japanese cities (Sapporo and Niigata) and a national surveillance collecting clinical information from pediatric endocrinologists throughout the country. During the last 10 years, one case of NC21-OHD was diagnosed by newborn screening in each city, resulting in incidences of 2.0 (95% confidence interval = 0.0-5.9) and 2.1 (0.0-6.2) per 1,000,000 in Sapporo and Niigata, respectively. We collected information from 85% of the 135 Councilors of Japanese Society of Pediatric Endocrinology. Fifteen NC21-OHD patients were diagnosed during childhood, resulting in the estimated prevalence of 0.58 (0.28-1.1) per 1,000,000. Eleven patients were discovered by newborn screening, 7 patients developed hyperandrogenism symptoms (2-8 years of age, median 7), and 9 patients were treated with hydrocortisone at the time of the survey. Ten out of 13 patients showed compound heterozygosity for the P30L mutation of CYP21A2. Our study suggests that the prevalence/incidence of NC21-OHD is lower than that in Western countries, and that the age for initial onset of androgen excess symptoms varies during the prepubertal period.