TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: HFAOP    
Fatty Acid Oxidation Gene Panel, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Follow up for abnormal biochemical results suggestive of a fatty acid oxidation disorder

 

Establishing a molecular diagnosis for patients with a fatty acid oxidation disorder

 

Identifying variants within genes known to be associated with a fatty acid oxidation disorder, allowing for predictive testing of at-risk family members

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Mitochondrial fatty acid beta-oxidation plays an important role in energy production, particularly in skeletal and heart muscle, and in hepatic ketone body formation. Disorders of fatty acid oxidation (FAO) are characterized by hypoglycemia, hepatic dysfunction, encephalopathy, skeletal myopathy, and cardiomyopathy. Most FAO disorders have a similar presentation and their biochemical diagnosis can, at times, be difficult. Commonly used metabolite screens such as urine organic acids, plasma acylcarnitines, and fatty acids are influenced by dietary factors and the clinical status of the patient. This often leads to incomplete diagnostic information or even false-negative results. Enzyme assays are limited to one enzyme per assay, which doesn't allow for comprehensive testing for all FAO disorders.

 

A comprehensive gene panel is a helpful tool to establish a diagnosis for patients with suggestive clinical and biochemical features, given the broad clinical spectrum and genetic heterogeneity of FAO disorders.

 

Acylcarnitine profile in plasma (ACRN / Acylcarnitines, Quantitative, Plasma) and urine organic acids (OAU / Organic Acids Screen, Random, Urine) are the recommended first-tier tests to assess individuals for a FAO disorder. Additional testing includes an assay in fibroblasts (FAO / Fatty Acid Oxidation Probe Assay, Fibroblast Culture), which is useful following molecular testing to determine whether variants of uncertain significance are pathogenic. The purpose of the in vitro probe assay is to offer screening for several defects of FAO and organic acid metabolism under controlled laboratory conditions using fibroblast cultures.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations:

Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at risk individuals.

 

To discuss the availability of further testing options, for assistance in general test selection, or for assistance in the interpretation of these results, Mayo Clinic Laboratory genetic counselors can be contacted at 800-533-1710.

 

Technical Limitations:

Next-generation sequencing (NGS) may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions, but assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If specific clinical disorders are suspected, evaluation by alternative methods can be considered.

 

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, these results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

There may be regions of genes that cannot be effectively amplified for sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

 

This assay will not reliably detect insertions/deletions (indels) of 40 or more base pairs (bp), including Alu insertions, long interspersed nuclear elements (LINES), and short interspersed nuclear elements (SINES). The bioinformatics software pipeline is verified to detect 95% of deletions up to 75 bp and insertions up to 47 bp. Additionally, low level mosaic variants may not be detected.

 

This test is not designed to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

 

Reclassification of Variants-Policy:

At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

 

Variant Evaluation:

Evaluation and categorization of variants is performed using published American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) recommendations as a guideline.(1) Other gene specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment. Intronic and synonymous sequence variants not predicted to impact splicing or otherwise contribute to disease are not reported.

Clinical Reference Recommendations for in-depth reading of a clinical nature

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. Vockley J, Bennett MJ, Gillingham MB: Mitochondrial fatty acid oxidation disorders. In: Valle D, Antonarakis S, Ballabio A, Beaudet A, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill Education; 2019. Accessed October 28, 2020. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=247995158&bookid=2709&Resultclick=2

Special Instructions Library of PDFs including pertinent information and forms related to the test