Testosterone Synthesis in Patients with 17β-Hydroxysteroid Dehydrogenase 3 DeficiencyIn a nationwide study on male pseudohermaphroditism among all pediatric endocrinologists and clinical geneticists in The Netherlands, 18 17betaHSD3-deficient index cases were identified, 12 of whom initially had received the tentative diagnosis androgen insensitivity syndrome AIS. The phenotypes and genotypes of these patients were studied. 17 beta-hydroxysteroid dehydrogenase type 3 deficiency diagnostic methods were evaluated in comparison to mutation analysis of the HSD17B3 gene. Amazon legal steroids studies were performed on testicular ribonucleic acid of patients homozygous for two different splice site mutations. The minimal incidence of 17betaHSD3 deficiency in The Netherlands and the corresponding carrier frequency were calculated. Haplotype analysis of the chromosomal region of the HSD17B3 gene in Europeans, North Americans, Latin Americans, Australians, and Arabs was used to ace tren trenbolone whether recurrent identical mutations were ancient or had repeatedly occurred de 17 beta-hydroxysteroid dehydrogenase type 3 deficiency. In genotypically identical cases, phenotypic variation for external dehydrohenase development was observed.
OMIM Entry - # - BETA HYDROXYSTEROID DEHYDROGENASE III DEFICIENCY
People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads testes. Their bodies, however, do not produce enough of the male sex hormone testosterone. Testosterone has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth. Most people with beta hydroxysteroid dehydrogenase 3 deficiency are born with external genitalia that appear female.
In some cases, the external genitalia do not look clearly male or clearly female sometimes called ambiguous genitalia. Still other affected infants have genitalia that appear predominantly male, often with an unusually small penis micropenis or the urethra opening on the underside of the penis hypospadias.
During puberty, people with this condition develop some secondary sex characteristics, such as increased muscle mass, deepening of the voice, and development of male pattern body hair. The penis and scrotum the sac of skin that holds the testes grow larger during this period. In addition to these changes typical of adolescent boys, some affected males may also experience breast enlargement gynecomastia.
Men with this disorder are generally unable to father children infertile. Children with beta hydroxysteroid dehydrogenase 3 deficiency are often raised as girls. About half of these individuals adopt a male gender role in adolescence or early adulthood.
Researchers have estimated that this condition occurs in approximately 1 in , newborns. It is more common in the Arab population of Gaza, where it affects 1 in to people. Mutations in the HSD17B3 gene cause beta hydroxysteroid dehydrogenase 3 deficiency. The HSD17B3 gene provides instructions for making an enzyme called beta hydroxysteroid dehydrogenase 3.
This enzyme is active in the testes, where it helps to produce testosterone from a precursor hormone called androstenedione. Mutations in the HSD17B3 gene result in a beta hydroxysteroid dehydrogenase 3 enzyme with little or no activity, reducing testosterone production. A shortage of testosterone affects the development of the reproductive tract in the male fetus, resulting in the abnormalities in the external sex organs that occur in beta hydroxysteroid dehydrogenase 3 deficiency.
At puberty, conversion of androstenedione to testosterone increases in various tissues of the body through processes involving other enzymes. The additional testosterone results in the development of male secondary sex characteristics in adolescents, including those with beta dehydrogenase 3 deficiency.
A portion of the androstenedione is also converted to the female sex hormone estrogen. Since impairment of the conversion to testosterone in this disorder results in excess androstenedione in the body, a corresponding excess of estrogen may be produced, leading to breast enlargement in some affected individuals.
This condition is inherited in an autosomal recessive pattern , which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Individuals who are genetically male and have two copies of a mutated gene in each cell are affected by beta hydroxysteroid dehydrogenase 3 deficiency. People with two mutations who are genetically female do not usually experience any signs and symptoms of this disorder. Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency. J Clin Endocrinol Metab. Clinical, endocrine, and molecular findings in 17beta-hydroxysteroid dehydrogenase type 3 deficiency.
Phenotypic variability in 17beta-hydroxysteroid dehydrogenase-3 deficiency and diagnostic pitfalls. Epub Apr Deleterious missense mutations and silent polymorphism in the human 17beta-hydroxysteroid dehydrogenase 3 gene HSD17B3.