3MCC Deficiency

Other Names

3MCC deficiency

3-methylcrotonyl-CoA carboxylase deficiency


MCC deficiency

Diagnosis Coding

E71.19, Other disorders 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 3-methylcrotonyl-CoA carboxylase (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 developmental delays or recurrent attacks of metabolic decompensation followed by complete recovery to asymptomatic adults. In most cases, the condition is relatively benign if properly recognized and treated. This enzyme requires biotin and elevated C5-OH can also be seen in biotinidase deficiency.


Approximately 1 in 50,000


Autosomal recessive

Prenatal Testing

DNA testing is 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 metabolic acidosis/hypoglycemia may still result in seizures and/or intellectual disability. Without treatment, recurring metabolic crises, associated with illness, may result in developmental delays, failure to thrive, or seizures. 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
  • Lethargy
  • Lab findings:
    • Hyperammonemia
    • Low carnitine levels
    • Ketoacidosis
    • Hypoglycemia
    • Hyperglycemia

If not treated promptly and consistently, patients may experience:
  • Failure to thrive
  • Fasting intolerance
  • Hypotonia
  • Reye-like illness
  • Seizures
  • Coma
  • Developmental delay/intellectual disability

Follow-up Testing after Positive Screen

Quantitative plasma acylcarnitine profile, serum biotinidase, urine organic acids, enzyme activity 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 - Information for Parents (STAR-G)).
  • Oral L-carnitine supplementation.
  • Fasting avoidance, low-protein diet in rare cases.
  • 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

3-Methylchrotonyl-CoA (3-MCC) Dehydrogenase Deficiency (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.

3MCC 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


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


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.

3-methylcrotonyl-CoA carboxylase deficiency (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.

Resources for 3MCC Deficiency (Disease InfoSearch)
Compilation of information, articles, and links to support; from Genetic Alliance.


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.

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.

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

Authors & Reviewers

Initial publication: July 2010; last update/revision: May 2019
Current Authors and Reviewers:
Author: Nicola Longo, MD, Ph.D.
Authoring history
2012: revision: Kimberly Hart, MS, LCGCA
2010: first version: Nicola Longo, MD, Ph.D.A
AAuthor; CAContributing Author; SASenior Author; RReviewer

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