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HelpTest ID: MCADZ Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency Full Gene Analysis, Varies
Reporting Name
MCAD Deficiency, Full Gene AnalysisUseful For
Confirmation of diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (as a follow-up to biochemical analyses)
Screening of at-risk carriers of MCAD deficiency when an affected relative has not had molecular testing
Diagnosis of MCAD deficiency in autopsy specimens
Clinical Information
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive inherited defect in the mitochondrial oxidation of fatty acids. The mitochondrial beta-oxidation pathway plays a major role in energy production, especially during periods of fasting and physical exertion. MCAD deficiency is prevalent among individuals of northern European origin, affecting 1 in 4900 to 1 in 17,000 individuals, with a carrier frequency estimated as high as 1 in 40 for some populations.
Phenotypic expression of MCAD deficiency is episodic in nature (ie, asymptomatic between attacks). Symptoms are typically precipitated by any stress (eg, fever, infection, vaccination) and mostly occur during the first 2 years of life, although some cases have been diagnosed in adulthood. Characteristic features of MCAD deficiency include: Reye-like syndrome (an acquired encephalopathy characterized by recurrent vomiting, agitation, and lethargy), fasting intolerance with vomiting, recurrent episodes of hypoglycemic coma, hypoketotic dicarboxylic aciduria, low plasma and tissue levels of carnitine, hepatic failure with fat infiltration (fatty liver), encephalopathy, and rapidly progressive deterioration leading to death. MCAD deficiency has also been associated with sudden infant death or sudden unexpected death syndrome.
Review of clinical features and biochemical analysis via plasma acylcarnitines (ACRN / Acylcarnitines, Quantitative, Plasma), fatty acid profile (FAO / Fatty Acid Oxidation Probe Assay, Fibroblast Culture), urine organic acids (OAU / Organic Acids Screen, Random, Urine), and urine acylglycines (ACYLG / Acylglycines, Quantitative, Urine) are always recommended as the initial evaluation for MCAD. If previously performed, the results of these biochemical assays should be included with the specimen as they are necessary for accurate interpretation of the MCAD sequence analysis.
The MCAD gene (ACADM) maps to 1p31 and has 12 exons, spanning 44 kb of DNA. Most variants are family-specific with the exception of the recurrent A->G transition at nucleotide 985 (985A->G). Among MCAD-deficient patients, approximately 52% are homozygous for the 985A->G pathogenic variant. The majority of the remaining patients are compound heterozygous for the 985A->G pathogenic variant and a different pathogenic variant.
Interpretation
All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
Testing Algorithm
For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
Report Available
14 to 20 daysDay(s) Performed
Varies
Clinical Reference
1. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424
2. Grosse SD, Khoury MJ, Greene CL, et al. The epidemiology of medium chain acyl-CoA dehydrogenase deficiency: An update. Genet Med. 2006:8(4):205-212
2. Ziadeh R, Hoffman EP, Finegold DM, et al. Medium chain acyl-CoA dehydrogenase deficiency in Pennsylvania: neonatal screening shows high incidence and unexpected mutation frequency. Pediatr Res. 1995;37(5):675-678
3. Roe CR, Coates PM: Mitochondrial fatty acid oxidation. In Scriver CR, Beaude AL, Sly WS, eds. The Metabolic and Molecular Bases of Inherited Disease. Vol 1. 7th ed. McGraw-Hill Book Company, 1995:1501-1533
Specimen Type
VariesShipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.
Submit only 1 of the following specimens:
Preferred:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Specimen Type: Cultured fibroblasts
Container/Tube: T-75 or T-25 flask
Specimen Volume: 1 Full T-75 or 2 full T-25 flasks
Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Specimen Type: Skin biopsy
Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [T115]).
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Specimen Type: Blood spot
Supplies: Card - Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Collection card (Whatman Protein Saver 903 Paper)
Acceptable: Ahlstrom 226 filter paper or blood spot collection card
Specimen Volume: 2 to 5 Blood spots
Collection Instructions:
1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information:
1. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.
2. For collection instructions, see Blood Spot Collection Instructions
3. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)
4. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)
Specimen Minimum Volume
Blood: 1 mL
Blood Spots: 5 punches, 3-mm diameter
All other specimen types: See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Special Instructions
Reference Values
An interpretive report will be provided.
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81479-Unlisted molecular pathology procedure
88233-Tissue culture, skin or solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| MCADZ | MCAD Deficiency, Full Gene Analysis | 95773-8 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 53971 | Result Summary | 50397-9 |
| 53972 | Result | 82939-0 |
| 53973 | Interpretation | 69047-9 |
| 53974 | Additional Information | 48767-8 |
| 53975 | Specimen | 31208-2 |
| 53976 | Source | 31208-2 |
| 53977 | Released By | 18771-6 |
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. Molecular Genetics: Biochemical Disorders Patient Information (T527)
3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.