Rare Nephrology News

Disease Profile

3-beta-hydroxysteroid dehydrogenase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

E25.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Adrenal hyperplasia 2; Adrenal hyperplasia II; 3b-hydroxysteroid dehydrogenase deficiency;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Female Reproductive Diseases;

Summary

3-beta-hydroxysteroid dehydrogenase (3BHSD) deficiency is a form of congenital adrenal hyperplasia, a group of conditions that interfere with the body's ability to make hormones. People with this condition lack many of the hormones made in the gonads (testes or ovaries) and the adrenal glands. There are three types of 3BHSD deficiency the salt-wasting form, non-salt-wasting form, and non-classic form. Signs and symptoms depend on the type of 3BHSD deficiency; the age at diagnosis; and the sex of the affected person. The salt-wasting form is the most severe type and can even be life-threatening. People with this form are generally diagnosed at birth due to symptoms related to abnormal salt reabsorption (i.e. dehydration, poor feeding, vomiting). Males with any form of the condition often have abnormalities of the external genitalia and are frequently infertile. Females with the condition may have slight genital abnormalities at birth, but often go on to experience irregular menstruation, hirsutism, and infertility as they get older. 3BHSD deficiency is caused by changes (mutations) in the HSD3B2 gene and is inherited in an autosomal recessive manner. Treatment varies but may include medications and/or surgery.[1][2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal oral glucose tolerance
0004924
Abnormal sex determination
0012244
Abnormality of the menstrual cycle
0000140
Accelerated skeletal maturation
Advanced bone age
Early bone maturation

[ more ]

0005616
Acidosis
0001941
Adrenocorticotropic hormone excess
0011749
Adrenogenital syndrome
0000840
Ambiguous genitalia, male
Ambiguous genitalia in males
0000033
Androgen insufficiency
0008226
Congenital adrenal hyperplasia
0008258
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Decreased circulating aldosterone level
Low blood aldosterone level
0004319
Decreased circulating cortisol level
Low blood cortisol level
0008163
Dehydration
0001944
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay

[ more ]

0000823
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Elevated circulating follicle stimulating hormone level
0008232
Elevated circulating luteinizing hormone level
0011969
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Female external genitalia in individual with 46,XY karyotype
0008730
Generalized hyperpigmentation
0007440
Hyperkalemia
Elevated serum potassium levels
0002153
Hypernatriuria
0012605
Hyponatremia
Low blood sodium levels
0002902
Hypotension
Low blood pressure
0002615
Hypovolemia
Depleted blood volume
0011106
Increased circulating ACTH level
High blood corticotropin levels
0003154
Increased circulating renin level
Elevated blood renin level
0000848
Male pseudohermaphroditism
0000037
Neonatal hypoglycemia
Low blood sugar in newborn
0001998
Osteoporosis
0000939
Perineal hypospadias
0000051
Premature adrenarche
0012412
Renal salt wasting
Loss of salt in urine
0000127
Urogenital sinus anomaly
0100779
Vomiting
Throwing up
0002013
30%-79% of people have these symptoms
Absence of secondary sex characteristics
0008187
Ambiguous genitalia, female
Atypical appearance of female genitals
0000061
Bifid scrotum
Cleft of scrotum
0000048
Clitoral hypertrophy
Enlarged clitoris
0008665
Decreased fertility in females
Reduced fertility in females
0000868
Decreased fertility in males
0012041
Decreased testicular size
Small testes
Small testis

[ more ]

0008734
Enlarged polycystic ovaries
Enlarged ovaries with cysts
0008675
Gynecomastia
Enlarged male breast
0000771
Hyperpigmented genitalia
Increased genital pigmentation
0030258
Insulin resistance
Body fails to respond to insulin
0000855
5%-29% of people have these symptoms
Abnormality of the labia majora
Abnormality of vaginal lips
0012881
Acne
0001061
Ectopic adrenal gland
Abnormal adrenal gland position
0011742
Hirsutism
Excessive hairiness
0001007
Percent of people who have these symptoms is not available through HPO
Absent scrotum
0008707
Adrenal hyperplasia
Enlarged adrenal glands
0008221
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia

[ more ]

0000062
Autosomal recessive inheritance
0000007
Hypospadias
0000047
Micropenis
Short penis
Small penis

[ more ]

0000054
Premature pubarche
Premature pubic hair growth
0012411

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    People with the salt-wasting form of 3-beta–hydroxysteroid dehydrogenase (3BHSD) deficiency need replacement of glucocorticoids, mineralocorticoids, and sex steroids. This may include:

    • Oral hydrocortisone (or other glucocorticoid) hydrocortisone tablets are the preferred choice for treatment. In children, premixed, oral suspensions of hydrocortisone and long-acting glucocorticoid preparations should be avoided.
    • Mineralocorticoid replacement by oral fludrocortisone acetate those with non–salt-losing forms do not need mineralocorticoid replacement.
    • Sex steroid replacement at puberty for those with a complete deficiency including testosterone in males and cyclic estrogenprogesterone therapy in females. This promotes development of secondary sexual characteristics in both males and females, and cyclic menstrual bleeding in females with normal female chromosomes.

    In people with late-onset (non-classic) 3BHSD deficiency, the need for replacement therapy varies depending on the severity of the condition. Glucocorticoid replacement suppresses excess male hormones (androgens) in children with premature onset of puberty. In pubertal and post-pubertal females with the late-onset form, glucocorticoid replacement alone may correct menstrual irregularities and infertility, and decrease hirsutism and acne.[3]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on 3-beta-hydroxysteroid dehydrogenase deficiency. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss 3-beta-hydroxysteroid dehydrogenase deficiency. Click on the link to view a sample search on this topic.

          References

          1. 3-beta-hydroxysteroid dehydrogenase deficiency. Genetics Home Reference. April 2015; https://ghr.nlm.nih.gov/condition/3-beta-hydroxysteroid-dehydrogenase-deficiency.
          2. Pang S. Congenital adrenal hyperplasia owing to 3 beta-hydroxysteroid dehydrogenase deficiency. Endocrinol Metab Clin North Am. March 2001; 30(1):81-99.
          3. J Paul Frindik. 3-Beta-Hydroxysteroid Dehydrogenase Deficiency. Medscape Reference. February 11, 2014; https://emedicine.medscape.com/article/920621-overview.

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