2M3HBA Deficiency

Other Names

HSD10 disease

2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency

MHBD deficiency

hydroxyl-CoA dehydrogenase deficiency

3-hydroxy-2-methylbutyryl-CoA dehydrogenase (3H2MBD) deficiency

2-methyl-3-hydroxybutyric acidemia

Diagnosis Coding

E71.118, other branched-chain organic acidurias

Disorder Category

An organic acidemia



Elevated C5:1 (methylcrotonyl or tiglyl carnitine) and elevated C5-OH (3-hydroxyisovaleryl carnitine)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=NA; specificity=NA


Deficiency of this mitochondrial enzyme results in impaired oxidation of certain fatty acids and isoleucine, with resultant accumulation of organic acids.


The condition is very rare, occurring in fewer than 1 in 1 million people. HSD10 Disease (Genetics Home Reference) The mutation has been identified in 17 families. [Zschocke: 2012]


X-linked, can affect females with a milder phenotype

Prenatal Testing

DNA testing is possible by amniocentesis or chorionic villus sampling (CVS) if the disease-causing mutation of an affected family member has been identified. Enzyme testing is possible by amniocentesis or CVS.

Other Testing

Genetic testing is possible for at-risk family members if both disease causing mutations of an affected family member have been identified.

Clinical Characteristics

With treatment, deterioration may be avoided, and some improvement may result. Without treatment, progressive loss of skills and neurologic impairment, mental retardation and seizures can be expected. Symptom onset has generally been between 9 and 14 months and may be aggravated by stress or illness.

Initial signs/symptoms may include:
  • Poor feeding
  • Spasticity
  • Lethargy
  • Lab findings:
    • Lactic acidosis
If not treated promptly, patients may experience:
  • Choreoathetosis
  • Progressive loss of motor skills
  • Hearing loss
  • Retinal degeneration
  • Seizures
  • Brain damage
  • Death

Follow-up Testing after Positive Screen

Quantitative plasma acylcarnitine profile, urine organic acids, enzyme assay in fibroblasts.

Primary Care Management

Upon Notification of the + Screen

If the Diagnosis is Confirmed

  • Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill.
  • Isoleucine and protein restriction, treatment of acute episodes with glucose and fluids.
  • For those identified after irreversible consequences, assist in management, particularly with low vision aids, hearing aids or cochlear implants, developmental and educational interventions.

Specialty Care Collaboration

Initial consultation and ongoing collaboration, particularly for dietary management. Genetic counseling for the family.


Information & Support

For Professionals

Newborn Screening ACT Sheets & Confirmatory Algorithms (ACMG)
ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results, membership required; American College of Medical Genetics.

2-methyl-3-hydroxybutyric aciduria (GARD)
Information and more links related to 2-methyl-3-hydroxybutyric aciduria, from the Genetic and Rare Diseases Information Center, National Institutes of Health.

Resources for 2M3HBA Deficiency (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.

2M3HBA Deficiency (OMIM)
Extensive review of literature providing technical information for providers on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

Genetics in Primary Care Institute (AAP)
Contains health supervision guidelines and other useful resources for the care of children with genetic disorders; American Academy of Pediatrics.

For Parents and Patients


Organic Acidemia Association (OAA)
A nonprofit organization that provides information, support, events, connections with other parents, a discussion board, and nutrition and recipe ideas.


HSD10 Disease (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; U.S. National Library of Medicine.

National Newborn Screening & Global Resource Center (NNSGRC)
Fact sheets, data reports, publications, and information for clinicians about genetic screening that includes links to state genetic contacts.


ACT Sheet for Elevated C5-OH Acylcarnitine (ACMG) (PDF Document 400 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Services for Patients & Families in Rhode Island (RI)

Genetics clinic services throughout the US can be found through the Genetics Clinic Services Search Engine (ACMG).
Genetics clinic services throughout the US can be found through the Genetics Clinic Services Search Engine (ACMG).

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Authors & Reviewers

Initial publication: March 2007; last update/revision: June 2012
Current Authors and Reviewers:
Author: Nicola Longo, MD, Ph.D.
Reviewer: Kimberly Hart, MS, LCGC

Page Bibliography

Zschocke J.
HSD10 disease: clinical consequences of mutations in the HSD17B10 gene.
J Inherit Metab Dis. 2012;35(1):81-9. PubMed abstract