ESPE Abstracts (2015) 84 P-3-780

aDepartment of Pediatrics and Adolescent Medicine, San Raffaele Hospital, University ‘Vita e Salute’, Milano, Italy; bDepartment of Cytogenetic and Molecular Biology, S. Chiara University Hospital, Pisa, Italy; cDepartment of Neonatology, S. Chiara University Hospital, Pisa, Italy; dAdolescent Medicine, Department of Pediatrics, S. Chiara University Hospital, Pisa, Italy; eEndocrine Laboratory, S. Chiara University Hospital, Pisa, Italy; fDivision of Pediatrics, San Giuseppe Hospital, Empoli, Italy

Background: The 5α-reductase-2 (5R2) deficiency is a rare 46, XY disorder of sex differentiation caused by mutations in the 5R2 gene. Diagnostic and clinical management is not well definite.

Aims and objectives: To describe relevant features of 5R2 deficiency in a large sample.

Methods: Retrospective records of persons with 5R2 deficiency were reviewed and clinical, endocrinological, genetic data analysed.

Results: A total of 25 individuals with certain diagnosis of 5R2 deficiency was collected (age at first clinical observation 0.4±1.0 years). About 50% had a misdiagnosis before diagnosis. Mean period from first observation to definitive diagnosis was 9.1±10.8 years. Gonadal removal was performed before certain diagnosis in eight subjects. Initial sex assignment was female in 64% and male in 36%. After diagnosis, sex re-assignment was performed in five babies: four girls to male sex and one boy to female sex. Baseline testosterone/DHT ratio was diagnostic in six/12 subjects, while post-hCG T/DHT ratio was diagnostic in all tested patients by setting the cut-off value at 15 or lower. 18 different mutations in 5R2 gene were identified (homozygous 12/25; compound heterozygous 11/25; monoallelic missense mutation 1/25; homozygous V89L variant associated with high progestin administration during pregnancy 1/25). Five mutations have never been reported (p.G13D, p.P79L, c.281+1G>A, c.331_332delCT, p.V124D). In some individuals, the same mutations were associated with different phenotypes.

Conclusions: Consistent time-lag may persist before the diagnosis of 5R2 deficiency is established. Sex assignment and gonadal removal may be done before certain diagnosis. Sex re-assignment is usually to male sex, but the contrary may occur. Accurate endocrine evaluation is recommended, since the use of appropriate cut-off values of T/DHT ratio may permit to select individuals with 5R2 deficiency. Large genetic variability is present and a clear genotype-phenotype correlation is lacking.

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