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Test ID: SCADZ Short-Chain Acyl-CoA Dehydrogenase (SCAD) Deficiency, Full Gene Analysis

Useful For

Preferred molecular analysis to confirm a diagnosis of short-chain acyl-CoA dehydrogenase deficiency (as a follow-up to the biochemical analyses only)

Testing Algorithm

See Newborn Screening Follow-up for Isolated C4 Acylcarnitine Elevations (also applies to any plasma or serum C4 acylcarnitine elevation) in Special Instructions.

Method Name

Polymerase Chain Reaction (PCR)/DNA Sequence Analysis

Reporting Name

SCAD Deficiency, Full Gene Analysis

Specimen Type

Varies


Specimen Required


Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

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 specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-25 flask

Specimen Volume: 2 Full flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

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 (T493)

Specimen Volume: 2 to 5 Blood Spots on collection card (Whatman Protein Saver 903 Paper; Ahlstrom 226 filter paper; or Blood Spot Collection Card, T493)

Collection Instructions:

1. An alternative blood collection option for a patient >1 year of age is finger stick.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry.

Additional Information:

1. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

2. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.


Specimen Minimum Volume

Blood: 1 mL
Blood Spots: 5 punches-3 mm diameter

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Clinical Information

Short-chain acyl-CoA dehydrogenase (SCAD) catalyzes the first step in the mitochondrial beta-oxidation of fatty acids with a chain length of 6 to 4 carbons. SCAD deficiency is a rare autosomal recessive condition. The clinical phenotype of SCAD shows considerable variability and is incompletely defined. Of those reported cases, hypoglycemia, developmental delay, and muscle hypotonia are the most common indicated features. The diagnosis of SCAD deficiency is challenging and should be based on the clinical presentation, 2 or more findings of ethylmalonic aciduria, and determination of fatty acid flux in fibroblasts indicating deficient SCAD activity. Molecular genetic analysis of the gene associated with SCAD (ACADS) may confirm the biochemical phenotype of SCAD deficiency.

 

The first step in evaluation for SCAD deficiency is identification of 2 or more findings of ethylmalonic aciduria, as determined by either OAU / Organic Acids Screen, Urine or ACYLG / Acylglycines, Quantitative, Urine. Ethylmalonic aciduria is a common, although not specific, laboratory finding in patients with SCAD deficiency. Determination of fatty acid flux in fibroblasts (FAO / Fatty Acid Oxidation Probe Assay, Fibroblast Culture) is warranted for an individual with 2 or more findings of ethylmalonic aciduria.

 

DNA sequencing of the ACADS gene is typically utilized only when SCAD deficiency is identified through biochemical analysis. The ACADS gene, associated with SCAD deficiency, is located on chromosome 12q22 and consists of 10 exons. Molecular genetic studies revealed that some patients carry ACADS gene mutations that cause complete absence of SCAD activity, while others carry ACADS gene variants (511C->T;625G->A) that may confer disease susceptibility only in association with other factors. The allele frequencies in the general population of the 511C->T and 625G->A gene variants are 3% and 22%, respectively. The presence of 2 of these gene variants is not considered an independent diagnostic marker for SCAD deficiency. Although further investigation is needed, it is most likely that these variants are not clinically significant.

 

Identification of 2 ACADS gene mutations that cause complete absence of SCAD activity alone is not sufficient to explain or determine possible clinical phenotype or prognosis. The clinical significance of carrying 2 mutations is often uncertain. Therefore, the results of ACADS gene sequencing for SCAD deficiency should be interpreted in light of the clinical presentation and biochemical findings in each case.

Reference Values

An interpretive report will be provided.

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.

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 May;17(5):405-424

2. Nagan N, Kruckeberg KE, Tauscher AL, et al: The frequency of short-chain acyl-CoA dehydrogenase gene variants in the US population and correlation with the C4-acylcarnitine concentration in newborn blood spots. Mol Genet Metab 2003 April;78:239-246

3. Corydon MJ, Vockley J, Rinaldo P, et al: Role of common gene variations in the molecular pathogenesis of short-chain acyl-CoA dehydrogenase deficiency. Pediatr Res 2001 January;49(1):18-23

4. van Maldegem BT, Duran M, Wanders RJ, et al: Clinical, biochemical, and genetic heterogeneity in short-chain acyl-coenzyme A dehydrogenase deficiency. JAMA 2006 August;296(8):943-952

Day(s) and Time(s) Performed

Performed weekly, varies

Analytic Time

14 days

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81405-ACADS (acyl-CoA dehydrogenase C-2 to C-3 short chain) (eg, short chain acyl-CoA dehydrogenase deficiency), full gene sequence

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SCADZ SCAD Deficiency, Full Gene Analysis In Process

 

Result ID Test Result Name Result LOINC Value
53123 Result Summary 50397-9
53124 Result No LOINC Needed
53125 Interpretation In Process
53126 Additional Information 48767-8
53127 Specimen 31208-2
53128 Source 31208-2
53129 Released By No LOINC Needed

Forms

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

2. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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