Introduction: Leydig cell hypoplasia (LCH) is a rare autosomal recessive condition that interferes with normal development of male external genitalia in 46,XY individuals. It is mediated by mutations in the luteinizing hormone receptor gene (LHCGR), most frequently located in the coding sequence, resulting in impairment of either LH/CG binding or signal transduction.
Case report: We report a 32-year-old female which presented with primary amenorrhea, female external genitalia and 46,XY karyotype. Breast and pubic hair development were B2 and PH2 respectively. Magnetic resonance imaging revealed inguinal testicles in the absence of uterus and ovaries. At first presentation serum luteinizing hormone (LH) was about threefold upper the normal limit while testosterone was in the female adult normal range. Estradiol was significantly low (10.6 pg/ml) and serum follicle-stimulating hormone was unremarkable. Dehydroepiandrosterone sulphate, 17-OH-progesterone and SHBG were normal. Anti-Müller-hormone and inhibin B were markedly elevated. Mutation or deletion of the SRY-, androgen receptor- and steroid 5-alpha-reductase-gene could be excluded. Finally, sequencing of the LHCGR gene revealed homozygote frameshift mutation in exon 10 (c.907C>T, p.Gln 303Trm). Furthermore, a second homozygote mutation was found (c.935A>G, p.Asn312Ser), although this mutation seemed to be of no clinical relevance, since it was located downstream the disruption of the gene sequence. We therefore concluded to the diagnosis of severe Leydig cell hypoplasia. A hormone replacement therapy with estradiol was inducted and the further operative removal of the inguinal testicles as well as the genetic analysis of the parents is planned.
Conclusions: This case-report is the first demonstrating two novel different homozygote mutations in the same hormone binding domain and therefore expands the genotypic spectrum of LHCGR mutations.
30 Apr - 04 May 2011
European Society of Endocrinology