Due to the non-specificity of symptoms in male neonates affected by salt-wasting (SW) CAH, it is hypothesised that a proportion die prior to diagnosis in countries lacking a newborn screening (NBS) programme, such as the UK. The aim of this study was to analyse 17-hydroxyprogesterone (17-OHP) in stored NBS blood spot samples, to detect undiagnosed cases of CAH. Samples were retrieved from storage for neonates who were born between 1994 and 2006, who subsequently died before 7 months of age. They were analysed, following anonymisation, for 17-OHP using the AutoDELFIA®. The control group comprised patients with SW-CAH, attending clinic, who gave consent for analysis of their stored NBS sample (n=37, 18 males, 19 females).
Using data provided by the Office for National Statistics, 1798 babies met the study group criteria. Of these, 1198 samples (67%) were retrieved and analysed following identification on NBS databases. Grouped according to gestational age and corrected for storage time, the mean and maximum bloodspot 17-OHP was as follows. Deceased full-term n=279, mean=6 nmol/L, max=107 nmol/L; deceased pre-term n=365, mean=28 nmol/L, max=251 nmol/L; deceased unknown gestational age n=553, mean=13 nmol/L, max=>394 nmol/L.
In the control group, there was evidence of hyponatraemia at presentation in all 18 males but only 16% of females. Of 18 NBS samples taken prior to commencing hydrocortisone (2 females, 16 males), the lowest level of 17-OHP was 179 nmol/L and 14 had levels greater than the highest standard (>268 to >420 nmol/L). Mutation analysis (8 common mutations) was performed for all samples from the deceased group with 17-OHP results >179 nmol/L (n=6, 3 males, 3 females) and no mutations were identified.
Therefore, despite evidence of increased morbidity (hyponatraemia) in affected males, we found no increase in mortality. In conclusion, this research does not support the hypothesis that, in our unscreened population, males affected by SW-CAH are dying prior to diagnosis.