A case of 11beta-hydroxylase deficiency detected in a newborn screening program by second-tier LC-MS/MS

Abstract

Background/aim: 21-Hydroxylase deficiency congenital adrenal hyperplasia (CAH) is one of the target diseases in many newborn screening programs. 11beta-Hydroxylase defiency is less frequent and does not cause salt-losing crisis. Thus, it is not a target disease for newborn screening. However, affected newborns might show slightly elevated levels of 17-OH-progesterone (17-OHP) in the standard immunoassay screening test. The objective is to show that the diagnosis of 11beta-hydroxylase deficiency can be done using a dried blood spot from newborn screening.

Case report: A male newborn was born at term. Blood sample for newborn screening was taken 36 h after birth. 17-OHP was slightly elevated using time-resolved fluorescence immunoassay (72.8 nmol/l; cut-off <60 nmol/l).

Results: We performed second-tier LC-MS/MS from the same blood sample and found elevated levels of 11-deoxycortisol and androstenedione and low cortisol. The family history was positive with an affected older sister born with ambiguous genitalia. Confirmation of diagnosis was done by hormonal analysis and molecular genetic testing of the CYP11B1 gene. A known CYP11B1 gene mutation W116C was identified in this family.

Conclusions: The diagnosis of 11beta-hydroxylase deficiency can be made by second-tier LC-MS/MS from dried blood spots. This method is very helpful in the work-up of elevated immunoassay 17-OHP.