Diagnosis; Screening

Establish or confirm diagnosis

Postmortem evaluation of individuals at any age who died suddenly or unexpectedly; testing is particularly recommended under the following circumstances (risk factors): -Family history of sudden infant death syndrome or other sudden unexpected deaths at any age -Family history of Reye syndrome -Maternal complications of pregnancy (acute fatty liver pregnancy, … Postmortem evaluation of individuals at any age who died suddenly or unexpectedly; testing is particularly recommended under the following circumstances (risk factors): -Family history of sudden infant death syndrome or other sudden unexpected deaths at any age -Family history of Reye syndrome -Maternal complications of pregnancy (acute fatty liver pregnancy, HELLP syndrome [hemolysis, elevated liver enzymes, and low platelet count]) -Lethargy, vomiting, fasting in the 48 hours prior to death -Allegation of child abuse (excluding obvious cases of trauma, physical harm) Macroscopic findings at autopsy: - Fatty infiltration of the liver - Dilated or hypertrophic cardiomyopathy - Autopsy evidence of infection that routinely would not represent a life-threatening event View more

Blood and bile are collected on the same filter paper card; newborn screening filter paper cards are used. Blood drawn into heparin-containing tubes and bile collected by direct puncture of the gallbladder are spotted on a filter paper card. Two circles are labeled and used for blood, 2 circles are … Blood and bile are collected on the same filter paper card; newborn screening filter paper cards are used. Blood drawn into heparin-containing tubes and bile collected by direct puncture of the gallbladder are spotted on a filter paper card. Two circles are labeled and used for blood, 2 circles are labeled and used for bile (each 25 mcL of volume). A 3/16" disk is punched out of the dried blood or 1/16" dried bile spot into an Eppendorf tube. The acylcarnitines are extracted by the addition of methanol and known concentrations of isotopically labeled acylcarnitines as internal standards. The extract is transferred to a Reacti-Vial, dried under a stream of nitrogen, and derivatized by the addition of n-butanol hydrochloric acid. The acylcarnitines are measured as their butyl esters by electrospray tandem mass spectrometry. The concentration of the analytes is established by computerized comparison of ion intensities of these analytes to that of the respective internal standards.(Chace DH, DiPerna JC, Mitchell BL, et al: Electrospray tandem mass spectrometry for analysis of acylcarnitines in dried postmortem blood specimens collected at autopsy from infants with unexplained cause of death. Clin Chem 2001;47:1166-1182; Miller MJ, Cusmano-Ozog K, Oglesbee D, Young S; ACMG Laboratory Quality Assurance Committee. Laboratory analysis of acylcarnitines, 2020 update: a technical standard of the American College of Medical Genetics and Genomics [ACMG]. Genet Med. 2021 Feb;23[2]:249-258) View more

Tests performed
Entire test performed in-house

Accuracy (clinical sensitivity) was assessed by analysis of known positive specimens; results were acceptable. Intra assay precision was performed with 5 replicates for blood samples and 10 replicates for bile samples, results were acceptable. Inter assay precision was performed over 2 days for blood and bile samples, results were acceptable.

Both blood and bile specimens must be collected in order to detect and independently confirm the largest possible number of disorders. However, if only one specimen type is available, testing is still beneficial. In cases with a higher level of suspicion due to the recognition of 1 or more risk … Both blood and bile specimens must be collected in order to detect and independently confirm the largest possible number of disorders. However, if only one specimen type is available, testing is still beneficial. In cases with a higher level of suspicion due to the recognition of 1 or more risk factors, collection of urine on filter paper and a skin biopsy is also recommended for further testing and enzymatic/molecular studies. Contact the Biochemical Genetic consultant or genetic counselor on call at 800-533-1710 to discuss high-risk cases. In comparison to living individuals, profiles of postmortem blood specimens generally show a nonspecific increase of short chain species. Patients with secondary carnitine deficiency may display uninformative acylcarnitine profiles in blood, but not in bile. Several fatty acid oxidation disorders are not associated with abnormal acylcarnitine profiles (eg, carnitine palmitoyltransferase I (CPT I) deficiency, 3-hydroxy-3-methylglutaryl CoA synthase (HMG-CoA synthase) deficiency) and will not be detected. View more

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Intra-Laboratory

Description of PT method: Help
Intra-laboratory alternative assessment of performance through quality control or patient blind testing

Description of internal test validation method: Help
This test was laboratory developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements.