5 Alpha Reductase Deficiency

The condition 5-alpha-reductase type 2 deficiency (5-ARD) is an autosomal recessive sex-linked condition resulting in the inability to convert testosterone to the more physiologically active dihydrotestosterone (DHT). A diagnosis of 5 alpha reductase deficiency syndrome was made after detail workup. Patient was counselled and in view that the patient was brought up as a female, decision of orchidectomy was done on 18.6.02. Postoperatively patient was fine and discharged on day 5 on ethinyloestradiol and asked to follow up on OPD basis. Cliteroplasty and urethral reconstruction was advised after a period of 1 year. The geneticist is responsible for verifying the karyotype and discussing with the family the autosomal dominant sex-linked nature of 5-ARD, which includes the recurrence risk of 1:8 for each subsequent pregnancy (50% of XY foetuses) and the potential for prenatal diagnosis.

Case Report

The condition 5-alpha-reductase type 2 deficiency (5-ARD) is an autosomal recessive sex-linked condition resulting in the inability to convert testosterone to the more physiologically active dihydrotestosterone (DHT) On Clinical examination : She was thin built, Height : 5 Feet 7 inches, Arm span : 187 cms.

Hair patterns : Upper lip-fine hair; Axillary hair : Pubic hair : coarse male pattern (tanner stage-3) there was significant hair on forearm and legs.

Breasts : No thelarche General condition appeared to be fair and all vitals were in normal limits. Respiratory and cardiovascular system were normal. Abdomen was soft.

External genitalia : No mons, Bilateral labiosacral folds seen, testis palpable in the folds, phallus length : 4.5 cms with prepuce over glans ventral frenulum, Grade 3 hypospadias, behind the urethra vaginal blind pouch - 6.5 cms length. On per rectal examination no mass palpable in pouch of Douglas suggestive of absent uterus.

Investigations : All routine investigations were within normal limits. Specific investigations were : Ultrasound of the abdomen and pelvis showed that uterus and ovaries were absent and posterior to the bladder approx. 5 cms blind vaginal pouch seen. Chromosomal analysis showed 46 XY karyotype, Serum testosterone : 389.75 ng/dl; Serum F.S.H. : 48.9 mIU/ml (0.9-15 mIU/ml); Serum L.H : 17.1 mIU/ml 91.3-13 mIU/ml); S. Testosterone : DHT ratio was also raised. A diagnosis of 5 alpha reductase deficiency syndrome was made. Patient was counselled and in view that the patient was brought up as a female, decision of orchidectomy was done on 18.6.02. Postoperative patient was fine and discharged on 5 on ethinyloestradiol and asked to follow up on OPD basis. Cliteroplasty and urethral reconstruction was advised after a period of one year.


Fig. 1 : Showing no breast development.

Fig. 2 : Showing bilateral labiosacral folds and phallus seen with absent mons.

Discussion

The condition 5-alpha-reductase type 2 deficiency (5-ARD) is an autosomal recessive sex-linked condition resulting in the inability to convert testosterone to the more physiologically active dihydrotestosterone (DHT). Since DHT is required for the normal masculinization of the external genitalia in utero, genetic males with 5-ARD are born with ambiguous genitalia (i.e, male pseudohermaphroditism).¹ A deficiency of the type 2 isozyme 5-alpha-reductase, which transforms testosterone to DHT, is the root cause of this disorder. The described clinical abnormalities range from infertility with normal male genital anatomy to underdeveloped male with hypospadias to predominantly female external genitalia, most often with mild clitoromegaly.

The uterus and fallopian tubes are absent due to the normal secretion of the mullerian-inhibiting factor. Testes are intact, as are wolffian structures (epididymis, vas deferens, seminal vesicles). Male internal ducts are present but terminate either in a blind pseudovaginal pouch or on the perineum.² This enzyme deficiency is not life threatening; however, if intra-abdominal testes are retained, an increased risk of gonadoblastoma exists. Secondary issues include a risk of osteoporosis if hormone replacement therapy is not initiated in the patient with a gonadectomy and psychological morbidity due to gender or sexual identity issues.³ The hallmark of 5-ARD is an elevated ratio in serum of the testosterone-to-DHT ratio (T/DHT). Ultrasound can verify the location of the testes and the absence of the uterus, which may be present in other conditions of the differential diagnosis.

Treatment

Medical : No medical treatment per se required in infancy and childhood. After gonadectomy, which should be performed prior to puberty. Either ethinyl oestradiol or conjugated oestrogens can be started at 13 yrs of age or when gonadotropins begin to rise. Providing appropriate psychosocial support for the child and family is important.³

Surgery : Feminizing genitoplasty. This surgery includes removal of the testes, restructuring of the labioscrotal folds into clear labia, and reduction or recession of the phallus to provide a more clitoral appearance.⁴ Vaginoplasty is required at some point for most patients who remain female.

References

1. Hochberg Z, Chayen R, Reiss N, et al. Clinical, biochemical, and genetic findings in a large pedigree of male and female patients with 5 alpha-reductase 2 deficiency. J Clin Endocrinol Metab 1996; 81 (8) : 2821-7.

2. Menodonca BB, Inacio M, Costa EM, et al. Male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency. Diagnosis, psychological evaluation, and management. Medicine (Baltimore) 1996; 75 (2) : 64-76.

3. Wilson BE, Reiner WG. Management of intersex : a shifting paradigm. J Clin Ethics 1998; 9 (4) : 360-9.

4. Forti G, Falchetti A, Santoro S, et al. Steroid 5 alpha-reductase 2 deficiency: virilization in early infancy may be due to partial function of mutant enzyme. Clin Endocrinol (Oxf) 1996; 44 (4) : 477-82.