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Genetics Home Reference: your guide to understanding genetic conditions
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17β-hydroxysteroid dehydrogenase type 10 deficiency

(often shortened to HSD10 deficiency)
Reviewed October 2009

What is HSD10 deficiency?

17β-hydroxysteroid dehydrogenase type 10 (HSD10) deficiency is a disorder that affects many parts of the body. This condition is typically more severe in males than in females. Males with HSD10 deficiency have normal early development but soon begin to lose skills they have acquired. This developmental regression typically occurs before age 5 and results in intellectual disability and loss of motor skills such as sitting, standing, and walking. Affected males frequently have weak muscle tone (hypotonia), recurrent seizures (epilepsy), and movement problems. Progressive vision and hearing loss is also common in males with HSD10 deficiency.

Females with HSD10 deficiency may have developmental delay, learning problems, or intellectual disability, but they do not experience developmental regression. Some females may have additional features of this condition, such as epilepsy, movement problems, and hearing loss.

How common is HSD10 deficiency?

The prevalence of HSD10 deficiency is unknown. At least 11 affected individuals have been identified.

What genes are related to HSD10 deficiency?

Mutations in the HSD17B10 gene cause HSD10 deficiency. This gene provides instructions for making an enzyme called HSD10, which is found in many areas of the body. The HSD10 enzyme is located within mitochondria, the energy-producing centers inside cells, where it has several different functions. This enzyme is involved in breaking down the protein building block (amino acid) isoleucine and a group of fats called branched-chain fatty acids. It is also necessary for certain chemical reactions involving male sex hormones (androgens), female sex hormones (estrogens), and substances called neurosteroids that regulate the activity of the nervous system.

Mutations that cause HSD10 deficiency change single amino acids in HSD10, which reduces or eliminates the activity of the enzyme. It remains unclear how a shortage (deficiency) of HSD10 enzyme leads to the signs and symptoms of this disorder. Some researchers suspect that the neurological problems associated with HSD10 deficiency are caused by abnormal neurosteroid activity. Other features of the disorder may be related to the inability to process isoleucine and certain fats.

Related Gene(s)

Changes in this gene are associated with 17β-hydroxysteroid dehydrogenase type 10 deficiency.

  • HSD17B10

How do people inherit HSD10 deficiency?

This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is usually sufficient to cause the disorder. However, some females with one mutation do not develop any signs or symptoms of the condition. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Where can I find information about diagnosis or management of HSD10 deficiency?

These resources address the diagnosis or management of HSD10 deficiency and may include treatment providers.

  • Gene Tests: 17-Beta-Hydroxysteroid Dehydrogenase X Deficiency (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/238914)

You might also find information on the diagnosis or management of HSD10 deficiency in Educational resources (http://ghr.nlm.nih.gov/condition/17beta-hydroxysteroid-dehydrogenase-type-10-deficiency/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/17beta-hydroxysteroid-dehydrogenase-type-10-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook.

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about HSD10 deficiency?

You may find the following resources about HSD10 deficiency helpful. These materials are written for the general public.

  • MedlinePlus - Health information

    • Health Topic: Metabolic Disorders (http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html)
    • Health Topic: Newborn Screening (http://www.nlm.nih.gov/medlineplus/newbornscreening.html)

  • Educational resources - Information pages

    • Iowa Department of Public Health (http://www.idph.state.ia.us/genetics/common/pdf/mhbd.pdf)
    • Medical Home Portal (http://www.medicalhomeportal.org/newborn/2m3hba-deficiency)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=35123)

  • Patient support - For patients and families

    • Children Living with Inherited Metabolic Diseases (CLIMB) (http://www.climb.org.uk/)
    • Family Village (http://www.familyvillage.wisc.edu/lib_acor.htm)
    • Organic Acidemia Association (http://www.oaanews.org/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Tests - Genetic tests ordered by healthcare professionals (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/238914)

  • ACT Sheets - Newborn screening follow up

    • Elevated C5-OH Acylcarnitine (http://www.ncbi.nlm.nih.gov/books/NBK55827/bin/C5-OH.pdf)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((2-methyl-3-hydroxybutyric%20aciduria%5BTIAB%5D)%20OR%20(2-methyl-3-hydroxybutyryl-coa%20dehydrogenase%20deficiency%5BTIAB%5D)%20OR%20(2m3hba%5BTIAB%5D)%20OR%20(3-hydroxy-2-methylbutyryl-coa%20dehydrogenase%20deficiency%5BTIAB%5D)%20OR%20(mhbd%20deficiency%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/300438)

What other names do people use for HSD10 deficiency?

  • 3H2MBD deficiency
  • 3-hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency
  • hydroxyacyl-CoA dehydrogenase II deficiency
  • 2M3HBA
  • 2-methyl-3-hydroxybutyric aciduria
  • 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency
  • MHBD deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about HSD10 deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding HSD10 deficiency?

acids ; aciduria ; amino acid ; androgens ; cell ; chromosome ; CoA ; deficiency ; dehydrogenase ; developmental delay ; enzyme ; fatty acids ; gene ; hormone ; hypotonia ; inheritance ; isoleucine ; methyl ; mitochondria ; motor ; motor skill ; muscle tone ; mutation ; nervous system ; neurological ; newborn screening ; prevalence ; protein ; regression ; screening ; seizure ; sex chromosomes ; sex hormone ; sign ; symptom ; trait ; X-linked dominant

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Ensenauer R, Niederhoff H, Ruiter JP, Wanders RJ, Schwab KO, Brandis M, Lehnert W. Clinical variability in 3-hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency. Ann Neurol. 2002 May;51(5):656-9. (http://www.ncbi.nlm.nih.gov/pubmed/12112118?dopt=Abstract)
  • Korman SH. Inborn errors of isoleucine degradation: a review. Mol Genet Metab. 2006 Dec;89(4):289-99. Epub 2006 Sep 6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16950638?dopt=Abstract)
  • Ofman R, Ruiter JP, Feenstra M, Duran M, Poll-The BT, Zschocke J, Ensenauer R, Lehnert W, Sass JO, Sperl W, Wanders RJ. 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency is caused by mutations in the HADH2 gene. Am J Hum Genet. 2003 May;72(5):1300-7. Epub 2003 Apr 14. (http://www.ncbi.nlm.nih.gov/pubmed/12696021?dopt=Abstract)
  • Olpin SE, Pollitt RJ, McMenamin J, Manning NJ, Besley G, Ruiter JP, Wanders RJ. 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency in a 23-year-old man. J Inherit Metab Dis. 2002 Oct;25(6):477-82. (http://www.ncbi.nlm.nih.gov/pubmed/12555940?dopt=Abstract)
  • OMIM: 17-BETA-HYDROXYSTEROID DEHYDROGENASE X DEFICIENCY (http://omim.org/entry/300438)
  • Perez-Cerda C, García-Villoria J, Ofman R, Sala PR, Merinero B, Ramos J, García-Silva MT, Beseler B, Dalmau J, Wanders RJ, Ugarte M, Ribes A. 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: an X-linked inborn error of isoleucine metabolism that may mimic a mitochondrial disease. Pediatr Res. 2005 Sep;58(3):488-91. Erratum in: Pediatr Res. 2006 Jan;59(1):162. Perez-Cerda, Celia [added]; Ribes, Antonia [added]. (http://www.ncbi.nlm.nih.gov/pubmed/16148061?dopt=Abstract)
  • Sass JO, Forstner R, Sperl W. 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: impaired catabolism of isoleucine presenting as neurodegenerative disease. Brain Dev. 2004 Jan;26(1):12-4. (http://www.ncbi.nlm.nih.gov/pubmed/14729408?dopt=Abstract)
  • Yang SY, He XY, Miller D. HSD17B10: a gene involved in cognitive function through metabolism of isoleucine and neuroactive steroids. Mol Genet Metab. 2007 Sep-Oct;92(1-2):36-42. Epub 2007 Jul 6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17618155?dopt=Abstract)
  • Yang SY, He XY, Olpin SE, Sutton VR, McMenamin J, Philipp M, Denman RB, Malik M. Mental retardation linked to mutations in the HSD17B10 gene interfering with neurosteroid and isoleucine metabolism. Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14820-4. doi: 10.1073/pnas.0902377106. Epub 2009 Aug 17. (http://www.ncbi.nlm.nih.gov/pubmed/19706438?dopt=Abstract)
  • Yang SY, He XY, Schulz H. 3-Hydroxyacyl-CoA dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease. FEBS J. 2005 Oct;272(19):4874-83. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16176262?dopt=Abstract)
  • Yang SY, He XY, Schulz H. Multiple functions of type 10 17beta-hydroxysteroid dehydrogenase. Trends Endocrinol Metab. 2005 May-Jun;16(4):167-75. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15860413?dopt=Abstract)
  • Zschocke J, Ruiter JP, Brand J, Lindner M, Hoffmann GF, Wanders RJ, Mayatepek E. Progressive infantile neurodegeneration caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: a novel inborn error of branched-chain fatty acid and isoleucine metabolism. Pediatr Res. 2000 Dec;48(6):852-5. (http://www.ncbi.nlm.nih.gov/pubmed/11102558?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2009
Published: February 11, 2013