17β-hydroxysteroid dehydrogenase 3 deficiency in a male pseudohermaphrodite

Abstract

Objective-To present the clinical, biochemical, and genetic features of a male pseudohermaphrodite due to 17beta-hydroxysteroid dehydrogenase 3 (17beta-HSD3) deficiency. Design-Case report. Setting-University teaching hospital Gynecology practicePatient(s)-A 15-year-old black American male pseudohermaphrodite with 17beta-HSD3 deficiency.Intervention(s)-Laboratory evaluation, genetic mutation analysis, bilateral gonadectomy, hormone replacement. Main Outcome Measure(s)-Endocrinologic evaluation and genetic analysis.Result(s)-A diagnosis of 17beta-HSD3 deficiency made on the basis of hormone evaluation was confirmed through genetic mutation analysis of the HSD17B3 gene. Female phenotype was attained after gonadectomy, passive vaginal dilatation, and hormone therapy. Conclusion(s)-17beta-HSD3deficiency was diagnosed in this patient based on endocrinologic evaluation and confirmed with genetic mutation analysis. The patient was able to retain her female sexual identity after surgical and medical treatment. Keywordspseudohermaphrodite; 17beta hydroxysteroid dehydrogenase 3 deficiency; 17-ketosteroid reductase deficiency

17β-Hydroxysteroid Dehydrogenase Type 3 Deficiency: Diagnosis, Phenotypic Variability and Molecular Findings

“…17-HSD3 deficiency is rare in Western countries, whereas in areas of high consanguinity, such as among the Gaza Strip Arab population, the incidence of 17-HSD3 deficiency has been reported to be 1 in 100-300 people (Rosler et al, 1996(Rosler et al, , 2006. Of the known cases of 17-HSD3 deficiency, most of the patients have been reported in Europe, Asia, Australia and South America, whereas only 11 cases have been reported in the United States (Mains et al, 2008;Moeller § Adamski, 2009). In a recent study from a gender assessment team in the United States that looked at DSD over a 25-year period, no patient with 17-HSD3 deficiency was diagnosed (Paris et al, 2007).…”

“…At the time of puberty, patients initially reared as females who have not undergone gonadectomy may have primary amenorrhea and varying degrees of virilization, including development of male body habitus, increased body hair and deepening of the voice (Faienza et al, 2007;Lee et al, 2007;Mains et al, 2008;Mendonca et al, 2000;Rosler et al, 1992;Rosler et al, 1996;). The clitoris can enlarge to as much as 5-8 cm in length due to peripheral conversion of T (Balducci et al, 1985;Mendonca et al, 2000;), but still remains smaller than a normal-sized penis and may be affected by chordee (Farkas § Rosler, 1993).…”

“…Once a diagnosis is suspected, molecular genetic studies can be used for definitive diagnosis. (Mains et al, 2008). The majority are missense mutations inherited as homozygous or compound heterozygous mutations, occurring most frequent in exons 3,9,10 of the gene; 4 are splice junction abnormalities (Andersson et al, 1996;Boehmer et al, 1999), 1 is a small deletion (777-783), and 1 is a thymidine deletion resulting in a frame shift mutation which alters the amino acid sequence from codon position 187 onward with a premature termination in codon 226 (Boehmer et al, 1999;Twesten et al, 2000).…”

“…The majority are missense mutations inherited as homozygous or compound heterozygous mutations, occurring most frequent in exons 3,9,10 of the gene; 4 are splice junction abnormalities (Andersson et al, 1996;Boehmer et al, 1999), 1 is a small deletion (777-783), and 1 is a thymidine deletion resulting in a frame shift mutation which alters the amino acid sequence from codon position 187 onward with a premature termination in codon 226 (Boehmer et al, 1999;Twesten et al, 2000). Two missense mutations, the 239 G to A resulting in an Arg to Gln (R80Q) substitution, which is the most frequent alteration described in the Arab population living in the Gaza Strip (Boehmer et al,1999;Mains et al, 2008;Rosler et al, 1996), and the 238 C to T resulting in an Arg to Trp (R80W) substitution (Bilbao et al, 1998;Faienza et al, 2007) involve the same arginine residue in exon 3 at position 80. This site has been extensively studied by systematic replacement of the wild-type arginine at position 80 and has been shown to be extremely important for both forming the salt bridge with the terminal phosphate moiety of the NADPH, as well as providing for a hydrophobic pocket for the purine ring of the adenosine portion of the NADPH (McKeever et al, 2002).…”

Clinical, hormonal, and molecular-genetic characteristics of two cases of abnormal sex formation (ASF) in 46XY subjects caused by type 3 17-beta hydroxysteroid dehydrogenase deficiency

“…Мутации чаще встречаются в экзонах 3, 9 и 10 [17]. Большинство мутаций приводит к полной потере ферментативной активности 17ГСД3.…”