Clinical, Biochemical and Morphologic Diagnostic Markers in an Infant Male Pseudohermaphrodite Patient with Compound Heterozygous Mutations (G115D/R246W) in SRD5A2 Gene

Vol. 62, No. 5, 2004

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Case Report

Clinical, Biochemical and Morphologic Diagnostic Markers in an Infant Male Pseudohermaphrodite Patient with Compound Heterozygous Mutations (G115D/R246W) in SRD5A2 Gene
Mónica Fernández-Cancio^a, Joan Rodó^b, Pilar Andaluz^a, María Jesús Martínez de Osaba^c, Francisco Rodríguez-Hierro^d, Cristina Esteban^a, Antonio Carrascosa^a, Laura Audí^a

^aUnidad Investigación Endocrinología y Nutrición Pediátricas, Hospital Vall d'Hebron,
^bServicio de Cirugía Pediátrica, Hospital Sant Joan de Déu,
^cServicio de Hormonología, Hospital Clínic and
^dServicio de Endocrinología Pediátrica, Hospital Sant Joan de Déu, Barcelona, España

Address of Corresponding Author

Horm Res 2004;62:259-264 (DOI: 10.1159/000081893)

Key Words

5-Reductase type 2 enzyme deficiency
SRD5A2 gene mutations
Male pseudohermaphroditism

Abstract

A patient with male pseudohermaphroditism and clinical diagnosis of partial androgen insensitivity in the neonatal period was studied at pubertal age for a molecular diagnosis. Hormone studies were conducted at baseline and under hCG stimulation for testosterone and dihydrotestosterone determinations at 2 months of age. Gonadectomy was performed at 4 months. At the age of 13 years genital skin fibroblasts were studied for androgen binding and 5 alpha -reductase activity and peripheral blood DNA was available for androgen receptor (AR) and 5 alpha -reductase (SRD5A2) gene analysis. Exons 1-8 of AR gene and exons 1-5 of SRD5A2 gene were sequenced. AR gene coding sequences were normal. SRD5A2 gene analysis revealed two heterozygote mutations (G115D and R246W), with the mother carrying the G115D and the father the R246W mutations. The compound heterozygote mutations in SRD5A2 gene explained an extremely low 5 alpha -reductase enzyme activity in genital skin fibroblasts. Revision of hormonal data from the neonatal period revealed an increased testosterone-to-dihydrotestosterone ratio at the end of an hCG stimulation test, which concurred with the molecular diagnosis. Testis morphology at 4 months of age was normal. Clinical and biochemical differential diagnosis between partial androgen insensitivity syndrome and 5 alpha -reductase enzyme deficiency is difficult in the neonatal period and before puberty. Our results show that in our patient the testosterone-to-dihydrotestosterone ratio would have adequately orientated the diagnosis. The two mutations in SRD5A2 gene have been described in patients of different lineages, though not in combination to date. Testis morphology showed that, during early infancy, the 5 alpha -reductase deficiency may not have affected interstitial or tubular development.

Author Contacts

Dr. Laura Audí
Unidad Investigación Endocrinología y Nutrición Pediátricas, Hospital Vall d'Hebron
Paseo Vall d'Hebron 119
ES-08035 Barcelona (Spain)
Tel. +34 93 489 40 30, Fax +34 93 489 40 30, E-Mail laudi@vhebron.net

Article Information

Received: December 16, 2003
Accepted: August 12, 2004
Published online: November 2, 2004
Number of Print Pages : 6
Number of Figures : 2, Number of Tables : 2, Number of References : 27

Medline Abstract (ID 15528927)

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