17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C>A) mutation in CYP17A1 gene

2015 ◽  
Vol 28 (7-8) ◽  
Author(s):  
Melikşah Keskin ◽  
Aylin Kılınç Uğurlu ◽  
Şenay Savaş-Erdeve ◽  
Elif Sağsak ◽  
Sare Gülfem Akyüz ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Congenital Adrenal Hyperplasia ◽  
Sex Steroids ◽  
Adrenocorticotropic Hormone ◽  
Delayed Puberty ◽  
Genetic Defects ◽  
Adrenal Hyperplasia ◽  
Rare Form ◽  
Lyase Deficiency ◽  
Enzymatic Defect

Abstract17α-Hydroxylase/17-20 lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia. Genetic defects causing combined 17OHD lead to the impaired production of cortisol and sex steroids, accumulation of mineralocorticoids, and compensatory overproduction of pituitary adrenocorticotropic hormone. Consequently, individuals with this enzymatic defect present with both adrenal cortical hyperplasia and variable degrees of hypertension, hypokalemia, and sexual immaturity. The patient was aged 15 years and 3 months and she was diagnosed with 17OHD while she was being evaluated for complaints of delayed puberty. In the present case, p.Y27*(c.81C>A) mutation was revealed in the sequence analysis of the

scholarly journals Hypertension and Hirsutism in a Young Female: A Rare Form of Congenital Adrenal Hyperplasia?

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A135-A136
Author(s):  
Preethi Polavarapu ◽  
Anupam Kotwal
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Free Testosterone ◽  
Dehydroepiandrosterone Sulfate ◽  
Young Female ◽  
Normal Serum ◽  
Adrenal Hyperplasia ◽  
Rare Form ◽  
Mineralocorticoid Receptor Antagonist ◽  
Heterosexual Intercourse ◽  
17 Hydroxyprogesterone

Abstract Background: Rare forms of congenital adrenal hyperplasia (CAH) especially can be a diagnostic and management challenge. We present a case of hypertension and hirsutism with elevated mineralocorticoid and sex steroid precursors concerning for non-classic rare form of CAH. Clinical Case: A 22 y/o female was evaluated in our endocrinology clinic for primary hypertension and hirsutism (modified Ferriman-Gallwey score of 12) but without menstrual irregularity, clitoromegaly or deepening of voice. Family history was significant for hypertension and hirsutism in her mother. Renal and pelvic ultrasonographies were normal. CT abdomen showed thickened bilateral adrenal glands. Case detection testing was positive with PAC/PRA of 19.4/0.4 however intravenous saline suppression test suppressed aldosterone to 5 ng/dL, hence ruled out primary aldosteronism. Cortisol suppressed to 0.6 mcg/dL after 1 mg overnight Dexamethasone, hence ruled out Cushing’s syndrome; prolactin and TSH were normal, serum HCG was undetectable. This prompted work up for other endocrine causes of hypertension and hirsutism which revealed follicular phase elevated dehydroepiandrosterone-sulfate of 772 mcg/dL (35–430), pregnenolone of 603 ng/dL (15–132), 17-hydroxypregnenolone of 1516 ng/dL (<226), 11-deoxycortisol of 39.4 ng/dL (<32); but normal 17-hydroxyprogesterone of 36.8 ng/dL (15–70), androstenedione of 1.12 ng/mL (0.26–2.14) and free testosterone of 26 ng/dL (9–44). 250-mcg ACTH administration stimulated cortisol to 24.6 mcg/dL, pregnenolone to 1478 ng/dL, 17-hydroxypregnenolone to 1716, 11-deoxycortisol to 64.2 ng/dL but 17-hydroxyprogesterone only stimulated to 59.9 ng/dL. We initiated spironolactone at 12.5 mg increased to 25 mg daily, which normalized her blood pressure. She was counseled regarding its teratogenicity but is she declined birth control, as she was not engaging in heterosexual intercourse. Urinary steroid analysis and genetic testing were pending. Conclusions: Hypertension and hirsutism accompanied by elevated pregnenolone, 17-hydroxypregnenolone, 11-deoxycortisol and dehydroepiandrosterone-sulfate, however, normal baseline as well as stimulated 17-hydroxyprogesterone, raise concern for co-occurrence of partial 3-betahydroxysteroid dehydrogenase deficiency in addition to non-classic 11-betahydroxylase deficiency. Management with mineralocorticoid receptor antagonist helped control hypertension.

VARYING EXPRESSION FOR SALT LOSING IN RELATED PATIENTS WITH CONGENITAL ADRENAL HYPERPLASIA

PEDIATRICS ◽  
1966 ◽  
Vol 38 (2) ◽  
pp. 215-219
Author(s):  
Arlan L. Rosenbloom ◽  
David W. Smith
Keyword(s):  
At Risk ◽  
Congenital Adrenal Hyperplasia ◽  
Genetic Defects ◽  
Adrenal Hyperplasia ◽  
Affected Sibling

Among 8 families in which more than one member had the salt losing manifestations of non-hypertensive virilizing congenital adrenal hyperplasia, there was a lack of expression for salt losing in an affected sibling in three families and in an affected first cousin in one family. The finding of differences in the expression for salt losing in related patients who are expected to have the same mutant alleles demonstrates that the salt losing and non-salt losing forms are not necessarily due to different genetic defects. This report emphasizes the importance of examining all siblings of an affected propositus and of considering all affected children to be at risk for the development of salt losing manifestations.

scholarly journals Influence of 17-Hydroxyprogesterone, Progesterone and Sex Steroids on Mineralocorticoid Receptor Transactivation in Congenital Adrenal Hyperplasia

2015 ◽  
Vol 83 (6) ◽  
pp. 414-421 ◽  
Author(s):  
Christiaan F. Mooij ◽  
Silvia Parajes ◽  
Karijn J. Pijnenburg-Kleizen ◽  
Wiebke Arlt ◽  
Nils Krone ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Sex Steroids ◽  
Mineralocorticoid Receptor ◽  
Adrenal Hyperplasia ◽  
17 Hydroxyprogesterone ◽  
Receptor Transactivation

scholarly journals A novel mutation in CYP17A1 gene leads to congenital adrenal hyperplasia: A case report

2019 ◽  
Author(s):  
Majid Nazari ◽  
Mohammad Yahya Vahidi Mehrjardi ◽  
Nosrat Neghab ◽  
Mahdi Aghabagheri ◽  
Nasrin Ghasemi
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Homozygous Deletion ◽  
Blood Levels ◽  
Primary Amenorrhea ◽  
Adrenal Hyperplasia ◽  
Lyase Deficiency

Background: Congenital adrenal hyperplasia is a rare autosomal recessive disorder where the mutation in P450 family 17 subfamily A member 1 gene (CYP17A1) is involved in its etiology. The disorder represents itself with low blood levels of estrogens, androgens, and cortisol that generally couples with hypertension, Hypokalemia, sexual primary amenorrhea, infantilism and in affected individuals. Case: In this study, the CYP17A1 gene in a 14-year-old female was examined. The karyotype of the patient was 46, XX, and the analysis of the CYP17A1 gene by Sanger sequencing revealed a novel homozygous deletion c.1052-1054CCT which led to isolated 17,20-lyase deficiency. Conclusion: In conclusion, this study report an in-frame deletion which results in isolated 17, 20-lyase deficiency, and the mutation might be used for diagnosis in other patients with distinctive clinical symptoms.

scholarly journals Precocious Pseudopuberty Due to a Rare Form of Congenital Adrenal Hyperplasia

1982 ◽  
Vol 19 (3) ◽  
pp. 145-150 ◽  
Author(s):  
W A Ratcliffe ◽  
J P McClure ◽  
W H R Auld ◽  
J W Honour ◽  
R Fraser ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Precocious Puberty ◽  
Gas Liquid Chromatography ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Rare Form ◽  
Specific Serum ◽  
Precocious Pseudopuberty ◽  
Basal Plasma ◽  
17 Hydroxyprogesterone

The biochemical investigation is described of a boy who presented with precocious puberty at the age of 3 years 9 months due to a rare form of congenital adrenal hyperplasia (CAH), steroid 11β-hydroxylase deficiency. Serum androgen levels were grossly elevated (17 hydroxyandrogens 10 nmol/l, androstenedione 129 nmol/l), 17 hydroxyprogesterone was modestly elevated (21 nmol/l), while serum gonadotrophins were low and testes were prepubertal in size. The major differential diagnosis was between an androgen-producing tumour and CAH. Initial serum and urine corticosteroid concentrations and their responses to dexamethasone were diagnostically misleading, later found to be due to lack of specificity of the radioimmunoassays and fluorimetric methods employed. Elevated basal plasma ACTH levels and suppression of androgen and ACTH levels by dexamethasone strongly suggested CAH. Definitive diagnosis of an 11β-hydroxylase defect was established by capillary column gas liquid chromatography of urine which demonstrated excess androgen and 11-deoxycortisol metabolites but no Cortisol metabolites. The diagnosis was confirmed by specific serum assays of 11-deoxycortisol, deoxycorticosterone, and Cortisol. The contribution of hormone assays and a protocol for their use in the diagnosis and monitoring of precocious puberty is discussed.

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