2M3HBA Deficiency

Other Names

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

Screening

Finding

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

Overview

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

Prevalence

Fewer than 10 reported cases [2M3HBA Deficiency Fact Sheet (Iowa Dept. of Health) (PDF Document 21 KB)]

Inheritance

X-linked, can affect females with a milder phenotype

Prenatal Testing

DNA testing possible by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified. Enzyme testing 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.

Resources

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.

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 that provides technical information on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

2M3HBA Deficiency Fact Sheet (Iowa Dept. of Health) (PDF Document 21 KB)
Provides information for parents and professionals.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

For Parents and Patients

Support

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

General

2M3HBA Deficiency (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; U.S. National Library of Medicine.

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

Tools

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

Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

See all Newborn Screening Programs services providers (3) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

For other services related to this condition, browse our Services categories or search our database.

Authors

Author: Nicola Longo, MD, PhD - 3/2007
Reviewing Author: Kimberly Hart, MS, LCGC - 6/2012
Compiled and edited by: Alfred Romeo, RN, PhD - 3/2007
Content Last Updated: 6/2012