3-Methylcrotonylglycinuria (3MCC) - MCCC1/MCCC2
Sequencing
3-Methylcrotonylglycinuria (3MCC) is an inborn error of
leucine metabolism caused by the deficiency of 3-methylcrotonyl-CoA
carboxylase. Patients are often identified via newborn screening. Mildly
affected or asymptomatic mothers with 3MCC deficiency have also been
identified via positive newborn screening in their children.
3MCC deficiency can be caused by a mutation in either the gene
coding the alpha subunit (MCCC1) or beta subunit (MCCC2) of the enzyme.
The presentation of this disorder is highly variable with severe cases
experiencing significant neurological abnormalities, psychomotor retardation,
seizures, cardio-respiratory failure and coma. Ketoacidosis, hypoglycemia and
hyperammonemia are often seen. Mild cases may be asymptomatic or display
fatigue, muscle weakness and/or mild developmental delay.
Sequencing of the MCCC1 and MCCC2 genes will
detect mutations in 99% of individuals with 3MCC deficiency and is available
from the Metabolic Laboratory of the Greenwood Genetic Center. Molecular testing
is useful to confirm the diagnosis and identify the disease causing mutations
within a family to allow for carrier testing and prenatal diagnosis.
Specimen requirements: 5 to 10 ml of peripheral blood
collected in an EDTA (lavendar top) Vacutainer tube is preferred. The minimal
blood needed for reliable DNA isolation is 3 ml. If necessary, ACD solution A
Vacutainer tubes (yellow top) may be submitted. Please contact the laboratory
for more information.
Transport: Please contact Tim Wood or the molecular
diagnostic lab coordinator (1-800-473-9411) for shipping information. The
specimen should be kept at room temperature and delivered via overnight
shipping. FedEx is preferred. If shipment is delayed by one or two days, the
specimen should be refrigerated and shipped at room temperature. Do not
freeze the specimen. Samples collected on Friday can be safely designated
for Monday delivery.
Analysis standards: Analysis will be complete within 4
weeks of sample receipt. The lab director assesses the quality and
interpretation of results. Technical staff members independently assess the
quality and interpretation of the test. The Greenwood Genetic Center Metabolic
Diagnostic Laboratory is CLIA certified and actively participates in CAP
proficiency surveys.
Reporting of Test Results: Test results with
interpretation will be mailed and/or faxed following completion of the test.
Verbal reports will be telephoned to the person(s) requesting the test when an
abnormal test result occurs. Consultation with the laboratory director and
explanations of testing protocols will be supplied upon request.
CPT Codes:
- MCCC1 - 83890, 83898 (x4), 83904 (x5), 83909 (x5), 83912
- MCCC2 - 83890, 83898 (x4), 83904 (x5), 83909 (x5), 83912
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