ESPE Abstracts (2018) 89 P-P3-353

A Novel Compound Heterozygous Mutation in CYP19A1 Resulting in Aromatase Deficiency with Normal Gonadotropin Levels and Ovarian Tissue

Sezer Acara, Ahu Paketçia, Hüseyin Onayb, Tufan Çankayac, Semra Gürsoyd, Bayram Özhane, Ayhan Abacıa, Erdener Özerf, Mustafa Olgunerg, Ece Böbera & Korcan Demira


aDivision of Pediatric Endocrinology, Dokuz Eylul University School of Medicine, Izmir, Turkey; bDepartment of Medical Genetics, Ege University School of Medicine, Izmir, Turkey; cDepartment of Medical Genetics, Dokuz Eylul University School of Medicine, Izmir, Turkey; dDepartment of Pediatric Genetics, Dokuz Eylul University School of Medicine, Izmir, Turkey; eDivision of Pediatric Endocrinology, Pamukkale University School of Medicine, Izmir, Turkey; fDepartment of Pathology, Dokuz Eylul University School of Medicine, Izmir, Turkey; gDepartment of Pediatric Surgery, Dokuz Eylul University School of Medicine, Izmir, Turkey


Introduction: Aromatase deficiency leading to virilization in mother and female fetuses during pregnancy is a rare disease. It is characterized by impaired estrogen production, increased gonadotropins, and ovarian cysts. Herein, we report a clinical phenotype of the virilized female due to a novel compound heterozygous mutation in CYP19A1.

Case report: A 4-month-old girl was referred due to cliteromegaly. Her mother had developed acne, hair loss, voice change, and hirsutism during pregnancy. She was born with a birthweight of 2710 gr at the 35th week of gestation. Her clitoris size had regressed after birth. The parents were no relatives. The physical examination revealed that her weight was 6.8 kg (0.36 SDS), length was 64 cm (0.48 SDS), a clitoral length of 1 cm, and posteriorly fused labia minora. Initial evaluations excluded congenital adrenal hyperplasia. Ultrasonography revealed a normal uterus and but no ovarian tissue. Gonadotropin levels were normal at the time of admission but increased by the age of 6 months (Table 1). Karyotype was identified as 46, XX and SRY was negative. The laparoscopic evaluation showed normal uterus and ovaries. The biopsy specimens from both gonads were histologically consistent with ovarian tissue and the karyotype analysis of this specimens revealed 46,XX. The diagnosis of aromatase deficiency was suspected and a previously unidentified compound heterozygote mutation in CYP19A1 [IVS10+1 G> A; p.R115Q (c.344 G> A)] was found. The parents were carriers. The in silico analyzes categorized the variant to be pathogenic. During the follow-up, the fusion at the posterior of the labium minus was surgically corrected and no ovarian cyst was observed with pelvic ultrasonography until now.

Table 1
16 days4 months6 months8 months11 months17 months
FSH (mIU/ml)6.47.0236.318.727.975.1
LH (mIU/ml)0.530.974.361.270.7715.64
Estradiol (pg/ml)5.0<20<20<20<20<20
Total testosterone (ng/dl)78<10<10---

Conclusions: Aromatase deficiency should also be considered even if the initial FSH and LH levels are normal and ovarian cysts are lacking.