Sanger Sequencing for Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
Information for Ordering
Acceptable Specimen Types
- Fresh blood sample: 3–6 mL EDTA; no time limitations associated with receipt
- Saliva: OGD-575 DNA Genotek collection kit; kits are provided upon request
- DNA extracted from lymphocyte cells: minimum volume of 25 µL containing 3 µg of DNA; A260/A280 ratio ≥1.8; must be extracted in a CLIA-certified or equivalent laboratory
Turnaround Time
- Blood, saliva, or DNA: Average of 15 working days
Price, CPT Codes, and Z Code
- Targeted exon 11 analysis: $250 USD institutional/self-pay price
- Full gene sequencing: $550 USD institutional/self-pay price
- CPT code: 81403, with reflex to 81406 as needed
- Z code: ZB6AI
Candidates for Testing
Individuals with an abnormal acylcarnitine profile, hypoglycemic episodes, lethargy, seizures, or a family history suggestive of medium-chain acyl-CoA dehydrogenase deficiency (MCADD).
Specimen Shipping and Handling
Please refer to the specimen requirements listed above.
Blood, saliva, and extracted DNA specimens should be shipped at room temperature. Do not ship specimens on ice.
Specimens must be packaged to prevent breakage. Absorbent material must be included to contain liquids if breakage occurs. Specimens must also be shipped in double watertight containers, such as a specimen pouch placed inside the shipping company's diagnostic envelope.
To request a collection kit, please complete the Collection Kit Request Form.
Before shipping a specimen, please contact the UAB Medical Genomics Laboratory by email at medgenomics@uabmc.edu or by phone at 205-934-5562. Please provide the specimen type, shipment date, and package tracking number so the laboratory can help ensure proper and timely receipt.
Required Forms
About
Disorder Background
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common disorder of mitochondrial fatty acid β-oxidation. Affected individuals often present after fasting or a common illness with hypoketotic hypoglycemia, vomiting, lethargy, and seizures. Additional manifestations may include encephalopathy, hepatomegaly, acute liver disease, skeletal myopathy, cardiomyopathy, and life-threatening metabolic decompensation.
Individuals are typically healthy at birth, with most presenting between 3 and 24 months of age, although later presentation into adulthood has been reported. Approximately 18–25% of affected individuals die during their first metabolic crisis. Once diagnosed, the prognosis is generally excellent when prolonged fasting is avoided.
ACADM is the only gene known to be associated with MCADD. The gene consists of 12 exons spanning more than 44 kb and encodes a protein of 421 amino acids. Disease prevalence is estimated to range from approximately 1 in 4,900 to 1 in 17,000 individuals, depending on the population studied. The common pathogenic variant c.985A>G (p.Lys329Glu) in exon 11 accounts for approximately 80–90% of disease-causing alleles identified through newborn screening programs. The carrier frequency for this variant is estimated to range from 1 in 40 to 1 in 100.
Test Description
Two testing strategies are available for ACADM analysis:
- MCD2: Targeted analysis of the common c.985A>G (p.Lys329Glu) variant in exon 11.
- MCD1: Comprehensive sequencing of the entire ACADM coding region.
Because the c.985A>G variant accounts for the majority of pathogenic alleles, targeted exon 11 analysis is performed first for most individuals. If the individual is heterozygous for the common variant or the variant is not detected, comprehensive sequencing of the ACADM gene is performed as a reflex test.
Parental testing is performed at no additional charge when parental specimens are submitted during the same week as the proband specimen. Specimens received later are processed as separate clinical tests and billed accordingly.
View references for this testing.
For more information, test requisition forms, or collection kits, please contact the UAB Medical Genomics Laboratory at 205-934-5562 or medgenomics@uabmc.edu.