Late diagnosis of 5alpha steroid-reductase deficiency due to IVS12A>G mutation of the SRD5a2 gene in an adolescent girl presented with primary amenorrhea

Abstract

The clinical spectrum of 5α-reductase deficiency, caused by mutations in the SRD5A2 gene, ranges from complete female appearance of the external genitalia at birth to nearly complete male phenotype. cAse rePOrt: A 14-year-old girl presented with primary amenorrhea (PA) and lack of breast development. she was 173 cm in height, had an increased amount of pubic hair and clitoromegaly (3 cm), with a 4 cm blind vaginal pouch. Gonads were palpable in the inguinal canal bilaterally and no uterus was identified on ultrasound. chromosomal analysis showed a 46,XY karyotype. the testosterone/DHt ratio was high (16.5) and further increased to 29.4 after stimulation with hcG, thus favouring the diagnosis of 5α-reductase deficiency. Since the issue of gender change was not considered, gonadectomy was performed followed by successful feminisation with hormonal replacement therapy. GeNetIc stUDIes: Molecular analysis of the SRD5A2 gene by DNA sequencing of all 5 exons revealed the presence of the splice mutation A>G at position -2 of the acceptor site of intron 1/exon 2 (Ivs1-2A>G) in homozygosity. both non-consanguineous parents were found to be heterozygotes for this mutation. cONcLUsIONs: Although rare, SRD5A2 gene defect should be suspected in any girl presenting with PA and virilisation at puberty. the Ivs1-2A>G mutation of the SRD5A2 gene predominates in Greek-Cypriot patients with 5α-reductase deficiency and very likely reflects a founder effect.

5-α-Reductase type 2 deficiency: is there a genotype-phenotype correlation? A review

“…It is important to highlight that the standard deviations of the average EMS values for these mutations were the highest among the three groups (Tables 1, 2, 3); thus, in patients carrying mutations belonging to this group, a genotype-phenotype correlation seems to be the most difficult to establish, masculinized external genitalia being the most predominant phenotype. The frequent Mediterranean IVS1-2A > G mutation, which is thought to abolish enzymatic activity, had a low EMS value (average 4) nearer to a female phenotype, as is expected for mutations that severely impair enzymatic activity [62,63].…”

“…Among the mutations shown in Tables 1 to 3, p.G34R and p.N160D are only found in Egyptians, p.L55Q has only been described in Turkish patients, p.G183S in Brazilian patients, and IVS1-2A>G with a 0.98% carrier frequency in the Cyprus population [63]. Other mutations such as p.G196S, p.Q126R, and p.H231R are widely distributed among Caucasians.…”

Clinical Study of Progesterone Combined with Vitamin B6 in the Treatment of Amenorrhea Endocrine Disorders Caused by Antipsychotics

“…Dopamine and prolactin have a mutual inhibitory effect, thereby reducing the prolactin content and prompting the patient to resume the menstrual cycle [ 28 , 29 ]. Therefore, the combined application of progesterone and vitamin B6 can adjust the hormone levels in patients with amenorrhea and promote the recovery of menstruation under the synergistic effect of the two [ 30 – 32 ]. The combination of progesterone and vitamin B in patients with amenorrhea caused by antipsychotic drugs can regulate the hormone secretion of patients, and the clinical application effect is better [ 33 ].…”

Genetic Analysis of 25 Patients with 5α‐Reductase Deficiency in Chinese Population

“…However, this mutation was prevalent in Egypt and had linkage disequilibrium with the V89L polymorphism, which indicated a founder effect of the p.Gly34Arg mutation among Egyptians [35]. A c.182-2 A>G mutation was detected in a set of siblings (patients 21 and 22); this mutation is common in Greek-Cypriot patients with 5α-reductase deficiency and is very likely to be the result of a founder effect [36,37]. Vilchis et al [38] analyzed 11 Mexican patients with steroid 5α-reductase 2 deficiency.…”