17-beta-hydroxysteroid dehydrogenase deficiency overview

17-beta-hydroxysteroid dehydrogenase deficiency Microchapters
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Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating 17-beta-hydroxysteroid dehydrogenase deficiency from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
Molecular Genetic Studies
Genotyping
X Ray
CT
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
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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 is initially described in 1971 by Saez and his colleagues.

Classification

• No sufficient data for classification of 17 beta hydroxysteroid dehydrogenase deficiency.

Pathophysiology

• 17-beta-hydroxysteroid dehydrogenase deficiency-3 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 testosterones production. The reduction of testosterones 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 alpha-hydroxylase 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-3 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 characteristics. There has been no phenotype to genotype correlation.

Pelvic X ray

• There are no pelvic x ray finding associated with 17 beta hydroxysteroid dehydrogenase 3 deficiency.

CT

• There are no CT scan finding associated with 17 beta hydroxysteroid dehydrogenase 3 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.

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.