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
Screening
Overview
Deficiency of this mitochondrial enzyme results in impaired oxidation of certain fatty acids and isoleucine, with resultant accumulation of organic acids.Incidence
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]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
- 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
- Contact the family and evaluate the infant for poor feeding, vomiting, or lethargy.
- Provide emergency treatment/referral for symptoms of hypoglycemia, metabolic acdosis, or seizures.
- To confirm the diagnosis, work with the following service(s): see all Newborn Screening Programs services providers (3) in our database.
- For evaluation and ongoing collaborative management, consult the following service(s): see all Pediatric Genetics services providers (4) in our database.
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.
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)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. It includes
health supervision guidelines and other useful resources; represents 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, support, events, connections with other parents, a discussion board,
and nutrition and recipe ideas.
General
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.
Tools
ACT Sheet for Elevated C5-OH Acylcarnitine (ACMG) (
400 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical
Genetics.
Services
Newborn Screening Programs
See all Newborn Screening Programs services providers (3) in our database.
For other services related to this condition, browse our Services categories or search our database.
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