3MCC Deficiency
Guidance for primary care clinicians receiving a positive newborn screen result
Description
In 3MCC deficiency, a lack of 3-methylcrotonyl-CoA carboxylase (usually present in the liver, fibroblasts, and leukocytes) impairs the breakdown 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 and can also be seen in biotinidase deficiency.
Clinical Characteristics
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.
- Poor feeding
- Vomiting
- Irritability
- Lethargy
- Lab findings:
- Hyperammonemia
- Low carnitine levels
- Ketoacidosis
- Hypoglycemia
- Hyperglycemia
- Failure to thrive
- Fasting intolerance
- Hypotonia
- Reye-like illness
- Seizures
- Coma
- Developmental delay/intellectual disability
Primary Care Management
Next Steps After a Positive Screen
- Contact the family and evaluate the infant for poor feeding, vomiting, or lethargy.
- Provide emergency treatment/referral for symptoms of hypoglycemia, metabolic acidosis, or seizures.
Confirming the Diagnosis
- To confirm the diagnosis of 3MCC deficiency, work with Newborn Screening Services (see NW providers [1]).
- Follow-up testing will include quantitative plasma acylcarnitine profile, serum biotinidase, urine organic acids, and enzyme activity assay in white blood cells.
If the Diagnosis is Confirmed
- For evaluation and ongoing collaborative management, consult Biochemical Genetics (Metabolics) (see NW providers [1]).
- 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).
- Once a diagnosis is confirmed, endocrine testing is completed. Then, long-term care requires a specialist team and testing on a repeating basis (endocrine testing and brain MRIs for males).
- 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.
Resources
Information & Support
Related Portal Content
After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive for
a newborn condition. Find information about A New Diagnosis - You Are Not Alone;
Caring for Children with Special Health Care Needs; Assistance in Choosing
Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a
Diagnosis.
Tools
ACT Sheet for Elevated C5-OH Acylcarnitine (ACMG) (
336 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive, along with resources
for consultation and patient education/support; from the American College of Genetics and Genomics
Confirmatory Algorithms for Elevated C5-OH (ACMG) ( 224 KB)
Basic steps involved in determining the final diagnosis of an infant with a positive newborn screen for this condition; American
College of Medical Genetics.
Services for Patients & Families Nationwide (NW)
| Service Categories | # of providers* in: | NW | Partner states (4) (show) | | NM | NV | RI | UT | |
|---|---|---|---|---|---|---|---|---|---|
| Biochemical Genetics (Metabolics) | 1 | 1 | 2 | 3 | 2 | ||||
| Medical Genetics | 1 | 2 | 5 | 4 | 7 | ||||
| Newborn Screening Services | 1 | 3 | 2 | 2 | 3 | ||||
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
Page Bibliography
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
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