2M3HBA Deficiency

Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

HSD10 disease
Hydroxyl-CoA dehydrogenase deficiency
MHBD deficiency
3-hydroxy-2-methylbutyryl-CoA dehydrogenase (3H2MBD) deficiency
2-methyl-3-hydroxybutyric acidemia
2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency

ICD-10 Coding

E71.118, Other branched-chain organic acidurias

Disorder Category

Organic acidemia

Screening

Abnormal Finding

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

Tested By

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

Description

With 2M3HBA deficiency, the deficiency of this mitochondrial enzyme results in impaired oxidation of certainfatty acids and isoleucine, with resultant accumulation of organic acids.

Clinical Characteristics

With treatment for 2M3HBA deficiency, deterioration may be avoided, and some improvement may result.
Without treatment, progressive loss of skills and neurologic impairment, intellectual disability, and seizures can be expected. Symptom onset has generally been between 9-14 months and may be aggravated by stress or illness.
Initial signs/symptoms of 2M3HBA deficiency 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

Incidence

2M3HBA deficiency is very rare, occurring in less than 1 in 1 million people.The mutation has been identified in 17 families. [Zschocke: 2012]

Inheritance

2M3HBA deficiency is X-linked and can affect females with a milder phenotype.

Primary Care Management

Next Steps After a Positive Screen

  • Contact the family and evaluate the infant for poor feeding, vomiting, or lethargy.
  • Provide emergency treatment/referral for symptoms of hypoglycemia, metabolic acidosis, or seizures.

Confirming the Diagnosis

If the Diagnosis is Confirmed

Resources

Information & Support

After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive for a newborn condition. Find information about A New Diagnosis - You Are Not Alone; Caring for Children with Special Health Care Needs; Assistance in Choosing Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a Diagnosis.

For Professionals

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

Support

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

Tools

RI ACT Sheet for ß-ketothiolase (BKT) deficiency (ACMG) (PDF Document 128 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive, along with resources for consultation and patient education/support; from the American College of Genetics and Genomics

Confirmatory Algorithms for Elevated C5-OH (ACMG) (PDF Document 224 KB)
Basic steps involved in determining the final diagnosis of an infant with a positive newborn screen for this condition; 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).

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