3MCC Deficiency

Other Names

3-methylcrotonyl-CoA carboxylase deficiency

3-methylcrotonylglycinuria

3MCC deficiency

MCC deficiency

Diagnosis Coding

E71.19, other disorders of branched-chain amino-acid metabolism

Disorder Category

An organic acidemia

Screening

Finding

Elevated C5-OH (acylcarnitine)

Tested By

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

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.

Incidence

Approximately 1 in 50,000

Inheritance

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

  • Contact the family and evaluate the infant for poor feeding, vomiting, or lethargy.
  • Provide emergency treatment/referral for symptoms hypoglycemia, metabolic acidosis, or seizures.
  • To confirm the diagnosis, work with the following service(s): see all Newborn Screening Programs services providers (1) in our database.
  • For evaluation and ongoing collaborative management, consult the following service(s): see all Pediatric Genetics services providers (2) 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 (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.

Resources

Information & Support

For Professionals

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 (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.

3MCC 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.

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

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.

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

Tools

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 in Nevada

Select services for a different state: ID, MT, NM, RI, UT
Genetics clinic services throughout the US can be found through the Genetics Clinic Services Search Engine (ACMG).

Newborn Screening Programs

See all Newborn Screening Programs services providers (1) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (2) 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

Authors & Reviewers

Initial Publication: August 2007; Last Update: June 2012
Current Authors and Reviewers (click on name for bio):
Author: Nicola Longo, MD, Ph.D.
Reviewer: Kimberly Hart, MS, LCGC

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