3MCC deficiency

Other Names

3-methylcrotonyl-CoA carboxylase deficiency


3MCC deficiency

MCC deficiency

Diagnosis Coding

270.3, Disturbances of branched-chain amino acid metabolism

Disorder Category

An organic acidemia



Elevated C5-OH (acylcarnitine)

Tested By

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


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.


Approximately 1 in 50,000


Autosomal recessive

Prenatal Testing

DNA testing possible by amniocentesis if both disease causing mutations of an affected family member have been identified.

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, 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 Testing after Positive Screen

Quantitative plasma acylcarnitine profile, serum biotinidase, urine organic acids, enzyme activity assay in lymphocytes or cultured 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 (see 3MCC Deficiency - Information 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 Collaboration

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


Information & Support

For Professionals

3MCC Deficiency - Information for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.

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.

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.

3MCC deficiency Acute Illness Protocol (NECMP)
A guideline for health care 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 literature that provides technical information 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. 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.

Utah Newborn Screening Program (UDOH)
Provides information about the program, related legislation, training for practices, and newborn conditions; Utah Department of Health.

For Parents and Patients

3MCC Deficiency - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.

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.

3MCC deficiency (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; U.S. National Library of Medicine.


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.

Helpful Articles

PubMed search for 3MCC deficiency and neonatal screening, last 10 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


Author: Nicola Longo, MD, PhD - 7/2010
Reviewing Author: Kimberly Hart, MS, LCGC - 6/2012
Compiled and edited by: Alfred Romeo, RN, PhD - 10/2007
Content Last Updated: 6/2012

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