Deficiency of 17-Ketoreductase Presenting Before Puberty

Abstract

The diagnosis of 17-ketoreductase deficiency is established in most patients at or after puberty when basal plasma androstenedione levels are high; data on prebubertal children are limited. Two infants with external female genitalia presented in infancy with inguinal herniae and palpable gonads. Both had a 46, XY karyotype, a short vagina, absent uterus, and a gonadal biopsy showing testicular tissue. The value of an hCG stimulation test in making the diagnosis of 17-ketoreductase deficiency was confirmed by a minimal plasma testosterone but marked androstenedione response. Androgen receptor deficiency based on studies in genital skin fibroblasts was demonstrated in one of the cases. We speculate that this is possibly the result of failed induction of receptors secondary to androgen deficiency. Though ‘tomboyish’ in behaviour, both children are reared as girls.

The testosterone:androstenedione ratio in male undermasculinization

“…A number of clinically diagnosed cases of AIS may not have a mutation in the AR or defects in AR binding. AR binding is assessed by studying AR concentration or binding affinity (Evans et al ., 1984) and reduced androgen exposure due to other disorders may affect AR concentration (Gregory et al ., 1993). Some AR abnormalities may reside in noncoding regions of the gene while androgen insensitivity may also arise from defects elsewhere in the androgen action pathway.…”