Newborn screening (NBS) can detect
21-hydroxylase deficiency (21-OHD), allowing for early treatment initiation. However, many patients present with adrenal crises or
hyponatremia at their first visit. Age (in days) of
hyponatremia development in infants with
salt-wasting (SW)-type 21-OHD remains unclear. Therefore, we determined the earliest age of
hyponatremia diagnosis in this retrospective observational study using medical records of 40 patients with classic 21-OHD in Niigata Prefecture, Japan, from April 1989 to March 2019. We determined the earliest diagnosis of
hyponatremia (serum
sodium levels < 130 mEq/L) and created a
sodium decrease rate model to estimate
hyponatremia development age. Of 23 patients with SW-type 21-OHD, 10 (43.5%) were identified during NBS; the earliest case to present with
hyponatremia was at day 7. Serum
sodium levels were significantly and negatively correlated with age in days, and
hyponatremia was estimated to develop at 6.6 d after birth. Genotype or serum
17-hydroxyprogesterone levels were not associated with
sodium decrease rate. Thus,
hyponatremia development age is earlier (within 7 d) than the previously described time-point (10-14 d) in infants with SW-type 21-OHD. Efforts to reduce the time lag from obtaining results to consultation may be required in patients with high
17-hydroxyprogesterone levels on NBS.