17-beta-hydroxysteroid dehydrogenase deficiency overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Abdulkerim Yassin, M.B.B.S[2]
Synonyms and keywords: 17-beta hydroxysteroid dehydrogenase III deficiency, 17-ketosteroid reductase deficiency of testis, 17-KSR deficiency, Neutral 17-beta-hydroxysteroid oxidoreductase deficiency, Male Pseudo hermaphroditism with gynecomastia, Testosterone 17-beta-dehydrogenase deficiency
Overview
17-beta-hydroxysteroid dehydrogenase deficiency is a rare autosomal recessive developmental disorder that affects male sexual development. Individuals with this condition are genetically male and have testes, but do not produce enough testosterone. The synthesis of testosterones is impaired and the levels in the serum is low which disrupts the formation of external male genitalia before birth. The affected individual is male with XY chromosomes with phenotype female or ambiguous external genitalia which is the external genitalia do not look clearly male or clearly female , characterized by clitoromegaly, posterior labioscrotal fusion and perineal blind vaginal pouch. Testes are located in inguinal or in the labioscrotal folds. The internal urogenital tract (epididymis, vasa deferential, seminal vesicles, ejaculatory ducts) is well developed; prostate and Müllerian structures are absent. Majority of cases do not present until puberty, at which time peripheral conversion of androgen precursors causes ongoing virilization. Although some patients with less severe defects are brought up as males, affected males are usually raised as girls. During puberty, the affected patients present with either primary amenorrhea or sudden onset of virilization and most of the affected individuals develop male secondary sex characteristics, such as increased muscle mass, deepening of the voice, and development of male pattern body hair. HSD17B3 gene mutations result in a 17-beta hydroxysteroid dehydrogenase 3 enzyme with decrease or no activity, reducing production of testosterone from androstenedione. Genetic analysis can confirm the diagnosis. Gonadectomy is recommended to prevent continuous virilization if a female gender identity is established. The risk of testicular neoplasia has not been determined, a point which should be discussed if patients choose to transition into a male gender role. All affected people with the disease are infertile.
Historical Perspectives
17 beta hydroxysteroid dehydrogenase III deficiency was initially described in 1971 by Saez and his colleagues.
Classification
There is no classification of 17 beta hydroxysteroid dehydrogenase deficiency.
Pathophysiology
17-beta-hydroxysteroid dehydrogenase deficiency is biochemically characterized by decreased levels of testosterone and increased levels of androstenedione as a result of the defect in conversion of androstenedione into testosterone.
Causes
HSD17B3 gene mutation causes 17-beta hydroxysteroid dehydrogenase deficiency results a decrease in testosterone production. The reduction of testosterone affects the development of male reproductive tract which results phenotypically female or ambiguous external genitalia.
Differentiating 17 Beta hydroxysteroid Dehydrogenase Deficiency from Other Diseases
17-beta-hydroxysteroid dehydrogenase deficiency should be differentiated from other diseases that cause ambiguous genitalia.
Epidemiology and Demographics
Although the precise incidence of 17βHSD-3 deficiency is unknown, a recent study from the Netherlands estimated the incidence around 1 in 147,000 newborns, with a calculated heterozygote frequency of 1 in 135.
Risk Factors
The potential risk factor for the development of 17 beta hydroxysteroid dehydrogenase 3 deficiency is positive family history.
Screening
There is insufficient evidence to recommend routine screening for 17-beta-hydroxysteroid dehydrogenase deficiency.
Natural History, Complications, and Prognosis
The characteristic phenotype at birth is an XY individual with female or ambiguous external genitalia. The majority of those affected have female external genitalia and consequently are raised as girls.
Diagnosis
History and Symptoms
17-beta-hydroxysteroid dehydrogenase deficiency is clinically characterized by either ambiguous external genitalia or complete female external genitalia at birth; As a consequence of impaired male sexual differentiation in 46 XY individuals.
Physical Examination
Majority of affected babies with 17-beta hydroxysteroid dehydrogenase 3 deficiency are born with external genitalia that appear female.
Laboratory Findings
Increased serum androstenedione and decreased serum testosterone/androstenedione ratios after hCG stimulation. The definitive diagnosis can be made from Genetic testing.
Molecular Genetic Studies
17-beta-hydroxysteroid dehydrogenase deficiency is inherited in an autosomal recessive pattern.
Genotyping
17-beta-hydroxysteroid dehydrogenase deficiency is a condition with genotypically male and phenotypically female or ambiguous genitalia characteristics. There has been no phenotype to genotype correlation.
X ray
There are no x-ray findings associated with 17-beta-hydroxysteroid dehydrogenase deficiency.
CT
There are no CT scan findings associated with 17-beta-hydroxysteroid dehydrogenase deficiency.
Ultrasound
Ultrasound of abdomen and pelvis showed absence of uterus or vagina.
Other Imaging Findings
MRI of the abdomen and pelvis revealed absence of the uterus or vagina with likely gonadal tissue in the inguinal canals bilaterally with a cyst having a single sac contiguous to the gonadal tissue on the right
Other Diagnostic Studies
There is no other diagnostic studies found.
Treatment
Medical Therapy
If the diagnosis of 17-beta-hydroxysteroid dehydrogenase deficiency is made at birth, gender assignment should be discussed, depending on the expected result of virilization genioplasty. Affected individuals who raised as male may virilize on their own or with the help of testosterone treatment. In female patients who underwent gonadectomy, appropriate intervention with estrogen therapy should be introduced at the time of puberty to induce secondary sexual characteristics.
Surgical Therapy
17-beta-hydroxysteroid dehydrogenase deficiency has a 28 % risk of germ cell tumor in disorder of sexual development. Consequently, close monitoring is warranted for an individual who is raised as a male rather than removing the gonads at the time of diagnosis.
Primary Prevention
There is no known method to prevent 17 beta hydroxysteroid dehydrogenase deficiency.
Secondary Prevention
There is no known method to prevent 17 beta hydroxysteroid dehydrogenase deficiency.