Timing of hyponatremia development in patients with salt-wasting-type 21-hydroxylase deficiency

Abstract

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.

Clinical guidelines for the diagnosis and treatment of 21-hydroxylase deficiency (2021 revision)

“…Therefore, one of the important symptoms of this condition in female neonates is virilization of the external genitalia. If the disease is not diagnosed during the early neonatal period in males or females, poor feeding and poor weight gain may occur, and an adrenal crisis may develop after the first week of life ( 13 , 14 ). 21-OHD is a disorder affecting not only growth and sexual maturation but also the quality and prognosis of life.…”

Thirty-Year Lessons from the Newborn Screening for Congenital Adrenal Hyperplasia (CAH) in Japan

“…Retrospective analysis of the follow-up survey of the NBS in Tokyo revealed that, in classical 21OHD patients, the serum Na and K levels linearly deteriorated with age in days, and the age when the regression lines reached Na < 130 mEq/L, K > 7 mEq/L approximately coincided at 11.1 and 12.3 days, respectively [ 13 ] ( Figure 3 ). The risk of developing severe salt wasting increases during the second week of life without a threshold, and, therefore, an early intervention, ideally during the first week of life, is desirable [ 13 , 18 , 19 ].…”