New Mutation in CYP17A1 Gene Causing Congenital Adrenal Hyperplasia

Presentation Number: SAT 364
Date of Presentation: April 1st, 2017

Milay Luis*1 and Christine A Resta2
16155 JUNCTION BOULEVARD, REGO PARK, NY, 2Maimonides Medical Center, Brooklyn, NY


Background: Congenital adrenal hyperplasia refers to a group of autosomal recessive disorders characterized by a genetic defect in the protein and enzymes involved in cortisol biosynthesis creating different clinical manifestations from increased or decreased mineralocorticoids and androgens depending on the site of the block. In the case of CYP17A1 deficiency the clinical manifestations are hypertension and hypokalemia due to the accumulation of cortisol precursors with mineralocorticoid activity upstream of the block, plus sexual infantilism due to inability to synthesize androgens and estrogens. Unlike most other forms of CAH, mineralocorticoid excess and high corticosterone production mitigate the clinical consequences of cortisol deficiency, and symptomatic adrenal insufficiency is rare

Clinical Case: A 21 year old woman from Ecuador initially seen in pediatrics endocrinology at the age of 18years for primary amenorrhea. Her initial physical exam showed height of 154.5 cm, normal blood pressure of 113/74mmHg, sexual characteristics tanner 1. Initial blood work were as follows: Cortisol 19.3 nmol/L (110-606), ACTH 56.1 pmol/L (1.32-11), corticosterone >10000 nmol/dL ( 1.7-37.3) 11 Deoxycortisol 4.21nmol/L (<3.09), testosterone <0.0347nmol/L( 0.07-1.56) estradiol <7.3pmol/L (follicular phase 143-1376, luteal phase 176-1615) FSH 30.9 IU/L ( follicular phase 2.5-10.2 mid cycle peak 3.1-17.7, luteal phase 1.5-9.1) LH 24.5 IU/L (follicular phase 1.9-12.5, mid cycle peak 8.7-76.3, luteal phase 10.0-54.7) progesterone 2.0nmol/L (follicular phase<3.2, luteal phase8.3-68.3) Aldosterone <0.02nmol/L ( <0.77)

pelvic sonogram : no ovaries seen, small uterus

Karyotype 46 XX. Genetic evaluation: homozygous mRNA.C334-336:3 bp duplication of AATC. Codon 113. (This has not been previously reported as a mutation causing CAH due to CYP17A1 deficiency)

She was started on low dose estradiol with plans to titrate up. Once there is sonographic evidence of significant uterine growth, the plan is to treat the CAH with methylprednisolone as a means of reducing the high level of adrenal-derived progesterone and therefore induce menses. Current physical exam shows secondary sexual characteristics tanner 2.

Conclusion: this is the first case reported with CYP17A1 with a mutation on the codon 113 that can cause CAH due to CYP17A1 deficiency without hypertension or potassium abnormalities.


Nothing to Disclose: ML, CAR