Home > Newborn Disorders > 3MCC deficiency

3MCC deficiency

Disorder Category

an organic acid disorder

Screening

Finding

elevated C5-OH (acylcarnitine)

Tested By

tandem mass spectrometry (MS/MS); sensitivity: 100%; specificity: NA [Schulze: 2003]

Names

3MCC deficiency

3-methylcrotonyl-CoA carboxylase deficiency

3-methylcrotonylglycinuria

3MCC deficiency

MCC deficiency

ICD-9

270.3, Disturbances of branched-chain amino acid metabolism

Overview

Lack of the enzyme (usually present in liver, fibroblasts, and leukocytes) impairs the break down of leucine resulting in metabolic acidosis and occasional hypoglycemia. The phenotype is extremely variable, ranging from patients presenting in infancy with severe neurological involvement and developmental delays to patients with recurrent attacks of metabolic decompensation followed by complete recovery to asymptomatic adults. This enzyme requires biotin and elevated C5-OH can be seen in biotinidase deficiency.

Prevalence

about 1/50,000

Inheritance

autosomal recessive

Prenatal Testing

by amniocentesis is available.

Clinical Characteristics

With treatment, normal development and IQ are possible. However, severe episodes of hypoglycemia may still result in seizures and/or mental retardation. Without treatment, recurring metabolic crises, associated with illness, may result in developmental delay/mental retardation, seizures, coma, or death. Symptoms generally begin after three months and before three years of age. Affected children may be healthy between metabolic crises. Some people remain completely asymptomatic.

Initial signs/symptoms may include:
  • poor feeding
  • vomiting
  • irritability
  • spasticity
  • lethargy
  • lab findings:
    • hyperammonemia
    • low carnitine levels
    • ketoacidosis
    • hypoglycemia

If not treated promptly and consistently, patients may experience:
  • failure to thrive
  • fasting intolerance
  • hypotonia
  • Reye-like illness
  • seizures
  • coma
  • developmental delay/mental retardation
  • death

Follow-up on positive screening test

Quantitative plasma acylcarnitine profile, serum biotinidase assay, urine organic acids, enzyme assay in white blood cells.

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 (see 3MCC deficiency info for parents (STAR-G))
  • Oral L-carnitine supplementation
  • Frequent feeding, low protein diet in most servere cases, avoidance of fasting
  • For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions

Specialty Care Management

Initial consultation and ongoing collaboration, particularly for dietary management. Genetic counseling for the family.

Resources

Information & Support

For Professionals

3MCC deficiency info for professionals (STAR-G)
On the Screening, Technology and Research in Genetics (STAR-G) site, one of a series of Disorder Fact Sheets for Professionals; structured list of information about the condition, with links to more information.

ACT Sheet for Elevated C5-OH Acylcarnitine (ACMG) (PDF Document 400 KB)
Developed by the American College of Medical Genetics, includes recommended responses to positive newborn screening test results, diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets and Confirmatory Algorithms (link elsewhere on this page) for more info and sheets on other conditions.

ACT Sheets and Confirmatory Algorithms (ACMG)
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.

3MCC deficiency Acute Illness Protocol (NECMP)
A guideline for healthcare professionals treating the sick infant/child who has previously been diagnosed with 3MCCD; developed under the direction of Dr. Harvey Levy, Senior Associate in Medicine/Genetics at Children’s Hospital Boston, and Professor of Pediatrics at Harvard Medical School, for the New England Consortium of Metabolic Programs.

Resources for 3MCC deficiency (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National Library of Medicine and the Genetic Alliance.

3MCC deficiency (OMIM)
Extensive review of the literature, including clinical features and genetics, from the Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University, providing technical information for providers on genetic disorders, links to MEDLINE, and links to other scientific information and sites.

Utah Newborn Screening Program
The site provides information and statistics about the program and related legislation, training for practices, and the conditions screened for.

For Parents and Patients

3MCC deficiency info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) site, providing information for parents about 3MCC and links to other sites including parent support groups.

Organic Acidemia Association (OAA)
A non-profit organization that provides information for parents and providers; newsletters; event information; connections with other parents; a listserv; a discussion board; information about nutrition and recipes; translation of their web pages into five other languages; hosting of the Propionic Acidemia Research Network and other research funds; and links to other sites.

3MCC deficiency (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference site.

Services

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

Newborn Screening Programs

Utah Newborn Screening Program, more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening

Pediatric Medical Genetics

See all Pediatric Medical Genetics services providers (3) in our database.

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

Helpful Articles

PubMed search for articles on 3MCC deficiency in the last 5 years.

Pasquali M, Monsen G, Richardson L, Alston M, Longo N.
Biochemical findings in common inborn errors of metabolism.
Am J Med Genet C Semin Med Genet. 2006;142C(2):64-76. PubMed abstract

Authors

Author: Nicola Longo MD, PhD, 7/2010
Compiled and edited by: Alfred Romeo RN, PhD, 10/2007
Content Last Updated: 7/2010

Page Bibliography

Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.
Pediatrics. 2003;111(6 Pt 1):1399-406. PubMed abstract