Andrea PASTORÁKOVÁ1, Robert PETROVIČ1, Zuzana PRIBILINCOVÁ2, Mária KNAPKOVÁ3, Jana MALOVÁ1, Zuzana VARCHULOVÁ NOVÁKOVÁ1, Daniel BÖHMER1, Ján CHANDOGA1
1Ústav lekárskej biológie, genetiky a klinickej genetiky LF UK a UNB, Lekárska fakulta Univerzity Komenského, Bratislava, prednosta doc. MUDr. D. Böhmer, PhD.
2 Detská klinika LF UK a NÚDCH, Národný ústav detských chorôb, Bratislava, prednostka prof. MUDr. Ľ. Podracká, CSc.
3Skríningové centrum novorodencov SR, Detská fakultná nemocnica s poliklinikou, Banská Bystrica, vedúca laboratória
RNDr. M. Knapková, PhD.
SUMMARY
Congenital adrenal hyperplasia is a group of autosomal-recessive hereditary diseases caused by enzymatic defects in the biosynthesis of steroid hormones, cortisol, aldosterone and androgens caused by adrenal cortex hyperplasia.
Diagnosis and substitution therapy are carried out in specialized centers. Prenatal corticosteroid therapy may be offered in indicated cases of female fetal involvement.
Pathogenic variant (mutation) in one of seven genes encoding particular enzyme of steroidogenesis is associated with various forms and degrees of the disease. The most frequent is 21-hydroxylase deficiency (mutations in the CYP21A2 gene) results in increased levels of 17-hydroxyprogesterone. This metabolite can be detected from dried blood spot, being used for mass neonatal screening performed in Slovakia since 2003.
Six additional genes may also be mutated leading to other types of disease: gene for 11ß-hydroxylase – CYP11B1, 17α-hydroxylase – CYP17A1, 3ß-hydroxysteroiddehydrogenase – HSD3B2, gene for steroidogenic acute regulatory protein – STAR, gene of cholesterol side-chain cleavage enzyme – CYP11A1 and cytochrome P450 oxidoreductase gene – POR.
The paper focuses on etiopathogenesis, clinical symptomatology, neonatal screening and laboratory molecular genetic diagnosis of disease in Slovakia since 2008. During this period molecular genetic diagnosis has elucidated the genetic cause of 162 patients in the 21-hydroxylase gene, including 14 rare mutations detected by sequencing of the CYP21A2 gene.
Key words: congenital adrenal hyperplasia, neonatal screening, cortisol, CYP21A2, CYP11B1, prenatal therapy.
Lek Obz, 2020, 69 (3): 112 – 121
