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Molecular testing in congenital adrenal hyperplasia due to 21 α ‐hydroxylase deficiency in the era of newborn screening
Author(s) -
Sarafoglou K,
Lorentz C P,
Otten N,
Oetting W S,
Grebe S K G
Publication year - 2012
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2011.01694.x
Subject(s) - fludrocortisone , congenital adrenal hyperplasia , 21 hydroxylase , mineralocorticoid , medicine , newborn screening , glucocorticoid , pediatrics , prenatal diagnosis , endocrinology , hydrocortisone , fetus , biology , genetics , pregnancy
Sarafoglou K, Lorentz CP, Otten N, Oetting WS, Grebe SKG. Molecular testing in congenital adrenal hyperplasia due to 21 α ‐hydroxylase deficiency in the era of newborn screening. Newborn screening (NBS) identifies the majority of classical [salt‐wasting (SW) and simple‐virilizing (SV)] cases of congenital adrenal hyperplasia (CAH) due to 21 α ‐hydroxylase (21 α ‐OHase) during the first days of life. Diagnosis of classical CAH is confirmed by follow‐up serum 17‐hydroxyprogesterone and/or the adrenocorticotropin stimulation test; however, neither test definitively distinguishes between the classical subtypes. After confirmation, all newborns are started on hydrocortisone (glucocorticoid) and fludrocortisone (mineralocorticoid) treatment. While initiating fludrocortisone treatment in classical CAH patients, independent of subtype and before SW signs or symptoms occur, prevents a life‐threatening SW crisis, it may later complicate distinguishing between the classical subtypes. Genotype–phenotype correlations in 21 α ‐OHase deficiency are excellent; however, molecular testing is not a regular part of the diagnostic workup. Molecular testing on 39 patients (25 identified by NBS) with an already established diagnosis of CAH identified 11 SW patients (8 identified by NBS) whose mutations suggested further biochemical and clinical reassessment of their subtype. Overall, SW accounted for 57.6% of our classical CAH patients, below the generally accepted figure that >75% of classical CAH are comprised of the SW form. In the era of NBS, molecular testing is a valuable supplemental tool identifying patients who may benefit from reassessment of their salt‐retaining ability.