New genetic causes of primary adrenal insufficiency
Authors:
R. Pomahačová 1; J. Sýkora 1; J. Zamboryová 1; P. Paterová 1; J. Dort 2; E. Dortová 2; I. Šubrt 3
Authors‘ workplace:
Dětská klinika Lékařské fakulty v Plzni, Univerzity Karlovy v Praze a Fakultní nemocnice Plzeň
1; Neonatologické oddělení Lékařské fakulty v Plzni, Univerzity Karlovy v Praze a Fakultní nemocnice Plzeň
2; Ústav lékařské genetiky Lékařské fakulty v Plzni, Univerzity Karlovy v Praze a Fakultní nemocnice Plzeň
3
Published in:
Čes-slov Pediat 2018; 73 (2): 100-103.
Category:
Case Report
Věnováno významnému životnímu jubileu prof. MUDr. Lidky Lisé, DrSc.
Overview
The most frequent form of congenital adrenal hyperplasia (CAH) is 21-hydroxylase deficiency. The uncommon forms of CAH are defects at the beginning of steroidogenesis in the adrenal glands leading to either congenital lipoid adrenal hyperplasia (CLAH) caused by defect of steroidogenic acute regulatory protein (StAR protein) or P450scc deficiency caused by defect of cholesterol side-chain cleavage enzyme (P450scc). A classic form of both CLAH and P450scc deficiency is characterized by a severe disorder of steroidogenesis in the adrenal glands and in the gonads. All newborns have female external genitalia. The life-threatening adrenal insufficiency is manifested early after birth. In the nonclassic forms of CLAH and P450scc deficiency is a partial loss of function of StAR protein or P450scc. The patients present with late onset of primary adrenal insufficiency and undervirilised external genitalia in male patients (micropenis, cryptorchidism, hypospadias).
We characterized a case of congenital adrenal insufficiency caused by P450scc deficiency. The patient presented after birth with cardiopulmonary instability, hyponatremia, hyperkalemia, hypoglycemia and metabolic acidosis. There were no signs of the external genitalia virilism. The replacement therapy with glucocorticoids and mineralocorticoids led to normal laboratory. At the age of 12 years, we confirmed hypergonadotropic hypogonadism, which revealed disorder of steroidogenesis in the adrenal glands and in the gonads. The genetic testing confirmed mutation in the CYP11A1 gene leading to deficiency of cholesterol side-chain cleavage enzyme. The patient is compound heterozygote for the novel CYP11A1 missense mutation c.412G>A (p.Gly138Arg) in exon 2 and frameshift mutation c.508_509delCT (p.Leu170Valfs*30) in exon 3. So far, only 29 patients with CYP11A1 mutations causing P450scc deficiency have been reported worldwide. There are no related reports in the Czech Republic.
Key words:
lipoid congenital adrenal hyperplasia, P450scc deficiency, steroidogenic acute regulatory protein (StAR protein), cholesterol side-chain cleavage enzyme (P450scc), STAR gene, CYP11A1 gene, primary adrenal insufficiency, gonadal deficiency
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Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
2018 Issue 2
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