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 (MedlinePlus) 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)
Includes information about symptoms, inheritance, diagnosis, finding a specialist, related diseases, and support organizations; Genetic and Rare Diseases Information Center of the National Center for Advancing Translational Sciences.

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

2M3HBA Deficiency (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

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 (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.


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 Montana (MT)

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: May 2018
Current Authors and Reviewers:
Author: Nicola Longo, MD, Ph.D.
Authoring history
2012: revision: Kimberly Hart, MS, LCGCR
2007: first version: Nicola Longo, MD, Ph.D.A
AAuthor; CAContributing Author; SASenior Author; RReviewer

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