17β-Hydroxysteroid Dehydrogenase Iii Deficiency

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Retrieved

2021-01-18

Source

Wikipedia

Trials

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Genes

HSD17B3, DECR1, HSD17B7, DHRS11, HSD17B13

Drugs

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17β-Hydroxysteroid dehydrogenase III deficiency is a rare autosomal recessive disorder of sexual development, or intersex condition, affecting testosterone biosynthesis by 17β-hydroxysteroid dehydrogenase III (17β-HSD III), which can produce impaired virilization (historically termed male pseudohermaphroditism) of genetically male infants.

Signs and symptoms

17-β-Hydroxysteroid dehydrogenase III 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, as well as:

Hypothyroidism
Cryptorchidism
Infertility
Abnormality of metabolism

Genetics

Genetically speaking, 17β-Hydroxysteroid dehydrogenase III deficiency is caused by mutations found in the 17β-HSD III (17BHSD3) gene.17β-HSD III deficiency is an autosomal recessive disorder.

Biochemistry

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Androstenedione

Androstenedione is produced in the testis, as well as the adrenal cortex. Androstenedione is created from dehydroepiandrosterone (DHEA) or 17-hydroxyprogesterone.

A deficiency in the HSD17B3 gene is characterized biochemically by decreased levels of testosterone and increased levels of androstenedione as a result of the defect in conversion of androstenedione into testosterone. This leads to a clinically important higher ratio of androstenedione to testosterone.

Diagnosis

In terms of the diagnosis of 17β-hydroxysteroid dehydrogenase III deficiency the following should be taken into account:

Increased androstenedione:testosterone ratio
Thyroid dyshormonogenesis
Genetic testing

Management

The 2006 Consensus statement on the management of intersex disorders states that individuals with 17β-hydroxysteroid dehydrogenase III deficiency have an intermediate risk of germ cell malignancy, at 28%, recommending that gonads be monitored. A 2010 review put the risk of germ cell tumors at 17%.

The management of 17β-hydroxysteroid dehydrogenase III deficiency can consist, according to one source, of the elimination of gonads prior to puberty, in turn halting masculinization.

Hewitt and Warne state that, children with 17β-hydroxysteroid dehydrogenase III deficiency who are raised as girls often later identify as male, describing a "well known, spontaneous change of gender identity from female to male" that "occurs after the onset of puberty." A 2005 systematic review of gender role change identified the rate of gender role change as occurring in 39–64% of individuals with 17β-hydroxysteroid dehydrogenase III deficiency raised as girls.

Society and culture

Modification of children's sex characteristics to meet social and medical norms is strongly contested, with numerous statements by civil society organizations and human rights institutions condemning such interventions, including describing them as "harmful practices".

Re: Carla (Medical procedure)

A 2016 case before the Family Court of Australia was widely reported in national, and international media. The judge ruled that parents were able to authorize the sterilization of their 5-year-old child. The child had previously been subjected to intersex medical interventions including a clitorectomy and labiaplasty, without requiring Court oversight - these were described by the judge as surgeries that "enhanced the appearance of her female genitalia". Organisation Intersex International Australia found this "disturbing", and stated that the case was reliant on gender stereotyping and failed to take account of data on cancer risks.