3MCC Deficiency
Other Names
3-methylcrotonyl-CoA carboxylase deficiency
3-methylcrotonylglycinuria
3MCC deficiency
MCC deficiency
Screening
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.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 (2) in our database.
- For evaluation and ongoing collaborative management, consult the following service(s): we currently have no Pediatric Genetics service providers listed, please search our Services database for related services.
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.
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. It includes
health supervision guidelines and other useful resources; represents a collaboration among the Health Resources & Services
Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.
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) (
400 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical
Genetics.
Services
Newborn Screening Programs
See all Newborn Screening Programs services providers (2) in our database.
Pediatric Genetics
We currently have no Pediatric Genetics service providers listed; search our Services database for related services.
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
| Author: | Nicola Longo, MD, Ph.D. - 7/2010 |
| Reviewing Author: | Kimberly Hart, MS, LCGC - 6/2012 |
| Compiled and edited by: | Alfred Romeo, RN, Ph.D. - 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