Introduction:
17-beta-hydroxysteroid dehydrogenase 3, or male pseudo hermaphroditism, is the other name for 17-ketosteroid reductase deficiency. In individuals suffering from 17-ketosteroid reductase deficiency, sexual development is altered. They are characterized by female or incompletely developed external genitalia in 46 XY individuals (males). It is associated with defective sex-hormone production, namely, testosterone, and the inadequate response of the tissue toward impaired testosterone production.
What Is Meant by Disorders of Sexual Development?
Disorders of sexual development comprise a group of genetic disorders in which a lack of synchronization exists between the expression of sexual characteristics, chromosome number, and gonads form. Earlier terminologies like pseudohermaphrodite, hermaphrodite, and intersex were used, but these terminologies have been replaced by the term disorders of sex development (DSD).
Following are a few recognized disorders of sex development:
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46 XX disorders of sexual development (these individuals have female genetic constituents, but they have a male appearance).
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Aromatase deficiency (reduced female sex hormones and increased male sex hormones).
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Glucocorticoid receptor gene mutation (disorder associated with the glucocorticoid receptor).
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Virilizing maternal tumors (human chorionic gonadotropin level increases in pregnancy which causes elevated androgen production).
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46 XY disorders of sexual development (a condition that occurs due to incomplete masculinization in intrauterine life).
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Denys-Drahs syndrome (abnormal kidney function is noted in this disorder).
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Campomelic syndrome (a genetic disorder affecting the baby’s development of lungs, airways, bones, and reproductive organs).
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Swyer syndrome (individuals suffering from this disorder have non-functional testes or ovaries).
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Leydig cell aplasia (this disorder affects male sexual development).
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17-ketosteroid reductase deficiency.
How Is 17-Ketosteroid Reductase Deficiency Caused?
Testosterone is produced through a biological process in which the cholesterol undergoes several biochemical changes under the influence of various enzymes and substrates and gets converted into testosterone. The mutations in genes involved in the production of the enzymes, and testosterone, lead to defective, insufficient, or altered production of this sex hormone. Researchers have identified five mutations that lead to defective testosterone production. The final step in testosterone production takes place in the testes.
The final step is a reversible biochemical step; in this last step, androstenedione (a steroid hormone that enhances the release of testosterone) is converted to testosterone, and the enzyme 17-ketosteroid reductase is responsible for this conversion. Individuals suffering from the deficiency of these enzymes have increased levels of androstenedione and reduced or limited levels of testosterone. This low level can be detected by analyzing the androstenedione to testosterone ratio (Androstenedione / Testosterone ratio) through a biochemical laboratory test, as androstenedione is also responsible for estrogen production. Therefore, increased quantity can lead to increased estrogen levels leading to the development of breasts at puberty in males (46 XY) affected by this genetic disorder.
Can a Child Get 17-Ketosteroid Reductase Deficiency From Their Parents?
17-ketosteroid reductase deficiency is an inherited genetic disorder with an autosomal recessive inheritance pattern. This means that the parents, the mother, and the father of the individual affected by 17-ketosteroid reductase deficiency carry the defective genes. Still, the parents do not show the symptoms of the disease. Genetic mutations (structural changes in the genes) are associated with 17-ketosteroid reductase deficiencies. There is a twenty-five percent chance or probability that parents who are carriers of the defective gene will have children with thalassemia. Genetic mapping in the prenatal stage can help doctors analyze the likelihood of the child suffering from 17-ketosteroid reductase deficiency.
What Are the Clinical Features Noted in Individuals Suffering From 17-Ketosteroid Reductase Deficiency?
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At Birth: The individuals, basically male (46 XY) suffering from this deficiency, show characteristics such as female genitalia or an incomplete or ambiguous female genital organ. Moreover, undescended testes, located near the labia majora (a part of the female genital organ), can be noted.
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At Puberty: The individuals show parts of reproductive organs that are Wolffian duct derivatives, such as epididymis, vas deferens, and seminal vesicles (male reproductive organs). Due to external female genitalia, most individuals suffering from this disorder are brought up as girls. As testosterone function is hampered, these individuals have male and female characteristics. Menstruation capability is not seen in these individuals, and the absence of menstruation at puberty is the marking point for diagnosing this genetic disorder caused due to 17-ketosteroid reductase deficiency.
What Are the Diagnostic Approaches for 17-Ketosteroid Reductase Deficiency?
Following are a few diagnostic approaches that help identify 17-ketosteroid reductase deficiency in an individual:
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Laboratory tests can be prescribed to check the levels of sex hormones, such as testosterone and luteinizing hormones. A reduced quantity or complete absence of testosterone, luteinizing hormones, or other androgenic sex hormones indicates that the individual has 17-ketosteroid reductase deficiencies.
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Tests to check for conditions like azoospermia (lack of sperm production) at puberty are also considered essential diagnostic criteria.
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If the individual has been raised as a girl since birth, lack of menstruation at puberty is an essential indicator of this disorder.
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On clinical examination, the doctor notes down the absence of development of facial hair, lack of voice maturation, or appearance as noted in gynecomastia (breasts development in males). These characteristics are pointed out to be necessary for the easy diagnosis of such disorders.
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Genetic tests that include genetic mapping, which helps identify the defective gene and its location in the defective gene in the chromosome, are prescribed. Genetic testing allows doctors to classify the exact type of sex development disorders, and as the cause and kind get identified, treatment protocols can be efficiently planned.
Diagnostic characteristics are identified by an expert doctor's clinical examination of the individual. These diagnostic procedures are done after taking consent from the parents and the individual to be diagnosed (excluding the infant):
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Testes cannot be palpated bilaterally; in other words, bilaterally absent testes are noted in individuals suffering from 17-ketosteroid reductase deficiency.
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The length of the male sex organ (penis) is examined in a full-term infant. If the size is less than 0.98 inches after fully stretching the organ (this condition is called a microphallus), then the presence of sex development disorders can be considered.
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Bifid scrotum (a cleft in the midline of the scrotum).
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Clitomegaly (enlargement of part of the female external genitalia, the clitoris).
What Are the Treatment Protocols Present for 17-Ketosteroid Reductase Deficiency?
Following are the treatment protocols that are being practiced at present:
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Hydrocortisone therapy is the initial treatment protocol. It targets maintaining the hormonal levels in affected individuals.
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In cases with adrenal insufficiency, fluid replacement therapy is advised.
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Surgeries can correct genital abnormalities.
Conclusion:
Psychological assurance in cases diagnosed with 17-ketosteroid reductase deficiency disorder is significant. As soon as abnormalities are noted in the child, the parents should be aware of their child's condition. Various government organizations and NGOs (non-government organizations) have created awareness regarding sex development disorders. Medical genetics advancement will surely help in the early diagnosis of these conditions and the genetic approaches for the treatment of these conditions.
