3-Methylcrotonylglycinuria: MCCC1/MCCC2 Sequencing

Turnaround Time

2 weeks

CPT Code(s)

81406 x2

Cost

$2,000

Genes

• 3-Methylcrotonylglycinuria I
• 3-Methylcrotonylglycinuria II

3-Methylcrotonylglycinuria (3MCC) is an autosomal recessive inborn error of leucine metabolism caused by the deficiency of 3-methylcrotonyl-CoA carboxylase. Patients are often identified through newborn screening. Mildly affected or asymptomatic mothers with 3MCC deficiency have also been identified through positive newborn screening in their children. 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. 3MCC can be caused by a mutation in either the gene coding the alpha subunit (MCCC1) or the beta subunit (MCCC2) of the enzyme.

Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.

Sanger Sequencing

Sequencing of the MCCC1 and MCCC2 genes will detect mutations in 99% of individuals with 3MCC.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA, dried blood spots, and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

The specimen should be kept at room temperature and delivered via overnight shipping. 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.

Prenatal diagnosis is available if the familial mutations are known. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.