ESPE Abstracts (2014) 82 P-D-3-1-952

Discordant Genotypic Sex and Concordant Phenotypes in Two Spanish Siblings with 17[alpha]-Hydroxylase/17, 20-Lyase Deficiency Carrying the Most Prevalent Mutated Alleles in Brazilian Patients

Laura Audía, Mónica Fernández-Cancioa, Marta Melón-Pardob & Emilio García-Garcíab


aPaediatric Endocrinology Unit, Vall d’Hebron Research Institute and Hospital, CIBERER, Autonomous University, Barcelona, Spain; bPaediatric Service, Hospital Virgen del Rocío, Sevilla, Spain


Background: 17α-Hydroxylase/17,20-lyase deficiency is a rare form of congenital adrenal hyperplasia caused by mutations in CYP17A1, characterized by reduction of androgens, estrogens and cortisol production and mineralocorticoid excess.

Objective and hypotheses: To describe the clinical and molecular characteristics of two sisters with 17α-hydroxylase/17, 20-lyase deficiency.

Method: Two sisters, phenotypic females, aged 17 and 15, the oldest with 46,XY and the youngest with 46,XX karyotypes, presented with primary amenorrhea and absent secondary sexual characteristics; the eldest presented elevated blood pressure. Both had elevated levels of ACTH, gonadotropins, progesterone, corticosterone and deoxycorticosterone, and reduced estradiol, testosterone, androstendione, 17-OH-P, DHEA-S, cortisol, aldosterone and renin activity.

Results: Mutational analysis identified compound heterozygous mutations (p.Arg362Cys/Trp406Arg) in CYP17A1 gene, previously described as the most prevalent mutations in Brazilian families of Spanish (p.Trp406Arg) or Portuguese (p.Arg362Cys) descent. The present siblings were born from parents with origins near Sevilla. They may represent the combination of the ancestral alleles for the most prevalent homozygous mutations in Brazil. The clinical and biochemical phenotypes agree with a complete lack of combined 17α-hydroxylase/17,20-lyase activities. Estrogen therapy and hydrocortisone were given in both cases and gonadectomy will be performed in the oldest.

Conclusion: Mutations in CYP17A1 should be investigated in patients with mineralocorticoid excess and deficiency of cortisol, androgens and estrogens. Regardless of genotypic sex, patients with combined 17α-hydroxylase/17,20-lyase deficiency are treated with glucocorticoids and estradiol.

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