Rhode Island Medical Home Portal

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

To confirm the diagnosis of 2M3HBA deficiency, work with Newborn Screening Services (see RI providers [2]).
Follow-uptesting will include quantitative plasma acylcarnitine profile, urine organic acids,andenzyme assay in fibroblasts.

If the Diagnosis is Confirmed

For evaluation and ongoing collaborative management, consult Medical Genetics (see RI providers [4]).
A dietician may work with the family to devise an optimal approach to dietary management. See Nutrition, Metabolic (see RI providers [15]).
Refer the family to Genetic Testing and Counseling (see RI providers [9]).
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, and developmental and educational interventions, such as Early Intervention for Children with Disabilities/Delays (see RI providers [15]).

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).

Service Categories	RI	NW		NM	NV	OH
Early Intervention for Children with Disabilities/Delays	15	4	36	33	4	56
Genetic Testing and Counseling	9	7	7	14	8	14
Medical Genetics	4	1	2	5	1	6
Newborn Screening Services	2	1	3	2	2	3
Nutrition, Metabolic	15	13	13	15	14	14

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.

Helpful Articles

PubMed search on 2M3HBA deficiency

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, LCGC^R

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