TY - JOUR
T1 - Difficulties in diagnosis and treatment of 5α-reductase type 2 deficiency in a newborn with 46,XY DSD
AU - Walter, Kerstin N.
AU - Kienzle, Frederike B.
AU - Frankenschmidt, Alexander
AU - Hiort, Olaf
AU - Wudy, Stefan A.
AU - Van Der Werf-Grohmann, Natascha
AU - Superti-Furga, Andrea
AU - Schwab, Karl Otfried
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/7
Y1 - 2010/7
N2 - Background/Aims: Steroid 5α-reductase deficiency (MIM*607306) caused by mutations in the SRD5A2 gene is characterized by a predominantly female phenotype at birth and significant virilization at puberty. The undermasculinization at birth results from low dihydrotestosterone (DHT) levels during fetal development as the type 2 isoenzyme activity is reduced. In puberty, when the type 1 isoenzyme activity increases, significant virilization occurs. Most 46,XY individuals with 5α-reductase 2 deficiency develop a male gender identity. Case Report and Results: We present a case with a predominantly female phenotype and ambiguous external genitalia but a normal 46,XY karyotype. Plasma steroid analysis after β-hCG stimulation at 8 days of age revealed a steroid profile estimated as normal with a testosterone (T)/DHT ratio of 9.5 initially misleading to the exclusion of 5α-reductase deficiency. However, mutation analysis of the SRD5A2 gene revealed a homozygote point mutation (Leu55Gln) confirming the diagnosis of 5α-reductase deficiency. A male phenotype was successfully achieved by hormone treatment with T and DHT after diagnosing 5α-reductase deficiency and a masculinization operation. As a side effect skeletal age accelerated temporarily. Conclusion: In individuals with predominantly female phenotype and suspected 5α-reductase deficiency, a T/DHT ratio during the neonatal period >8.5 might point to 5α-reductase deficiency. After confirmation of the diagnosis by molecular analysis of the SRD5A2 gene, a satisfactory change to a male phenotype can be achieved by hormone treatment preceding surgery.
AB - Background/Aims: Steroid 5α-reductase deficiency (MIM*607306) caused by mutations in the SRD5A2 gene is characterized by a predominantly female phenotype at birth and significant virilization at puberty. The undermasculinization at birth results from low dihydrotestosterone (DHT) levels during fetal development as the type 2 isoenzyme activity is reduced. In puberty, when the type 1 isoenzyme activity increases, significant virilization occurs. Most 46,XY individuals with 5α-reductase 2 deficiency develop a male gender identity. Case Report and Results: We present a case with a predominantly female phenotype and ambiguous external genitalia but a normal 46,XY karyotype. Plasma steroid analysis after β-hCG stimulation at 8 days of age revealed a steroid profile estimated as normal with a testosterone (T)/DHT ratio of 9.5 initially misleading to the exclusion of 5α-reductase deficiency. However, mutation analysis of the SRD5A2 gene revealed a homozygote point mutation (Leu55Gln) confirming the diagnosis of 5α-reductase deficiency. A male phenotype was successfully achieved by hormone treatment with T and DHT after diagnosing 5α-reductase deficiency and a masculinization operation. As a side effect skeletal age accelerated temporarily. Conclusion: In individuals with predominantly female phenotype and suspected 5α-reductase deficiency, a T/DHT ratio during the neonatal period >8.5 might point to 5α-reductase deficiency. After confirmation of the diagnosis by molecular analysis of the SRD5A2 gene, a satisfactory change to a male phenotype can be achieved by hormone treatment preceding surgery.
UR - http://www.scopus.com/inward/record.url?scp=77954788874&partnerID=8YFLogxK
U2 - 10.1159/000313372
DO - 10.1159/000313372
M3 - Journal articles
C2 - 20395661
AN - SCOPUS:77954788874
SN - 1663-2818
VL - 74
SP - 67
EP - 71
JO - Hormone Research in Paediatrics
JF - Hormone Research in Paediatrics
IS - 1
ER -