Isolated 17,20-lyase deficiency


Isolated 17,20-lyase deficiency, also called isolated 17,20-desmolase deficiency, is a rare endocrine and autosomal recessive genetic disorder which is characterized by a complete or partial loss of 17,20-lyase activity and, in turn, impaired production of the androgen and estrogen sex steroids. The condition manifests itself as pseudohermaphroditism in males, in whom it is considered to be a form of intersex, and, in both sexes, as a reduced or absent puberty/lack of development of secondary sexual characteristics, resulting in a somewhat childlike appearance in adulthood.
Unlike the case of combined 17α-hydroxylase/17,20-lyase deficiency, isolated 17,20-lyase deficiency does not affect glucocorticoid production, and for that reason, does not result in adrenal hyperplasia or hypertension.

Symptoms

The symptoms of isolated 17,20-lyase deficiency, in males, include pseudohermaphroditism, female gender identity, and, in non-complete cases of deficiency where partial virilization occurs, gynecomastia up to Tanner stage V ; in females, amenorrhoea or, in cases of only partial deficiency, merely irregular menses, and enlarged cystic ovaries ; and in both sexes, hypergonadotropic hypogonadism, delayed, impaired, or fully absent adrenarche and puberty with an associated reduction in or complete lack of development of secondary sexual characteristics, impaired fertility or complete sterility, tall stature, eunuchoid skeletal proportions, delayed or absent bone maturation, and osteoporosis.

Cause

Isolated 17,20-lyase deficiency is a rare disorder caused by genetic mutations in the gene CYP17A1, while not affecting 17α-hydroxylase. Isolated 17,20 lyase deficiency is a rare disease with only a small number of confirmed reports due to mutations in the CYP17A1 gene.
Observed physiological abnormalities of the condition include markedly elevated serum levels of progestogens such as progesterone and 17α-hydroxyprogesterone, very low or fully absent peripheral concentrations of androgens such as dehydroepiandrosterone, androstenedione, and testosterone and estrogens such as estradiol, and high serum concentrations of the gonadotropins, follicle-stimulating hormone and luteinizing hormone .

Diagnosis

Treatment

Males and females may be treated with hormone replacement therapy, which will result in normal sexual development and resolve most symptoms. In the case of 46,XY individuals who are phenotypically female and/or identify as the female gender, they should be treated with estrogens instead. Removal of the undescended testes should be performed in 46,XY females to prevent their malignant degeneration, whereas in 46,XY males surgical correction of the genitals is generally required, and, if necessary, an orchidopexy may be performed as well. Namely in genetic females presenting with ovarian cysts, GnRH analogues may be used to control high FSH and LH levels if they are unresponsive to estrogens.