Test Catalog

Test Id : PMSBB

Postmortem Screening, Bile and Blood Spot

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

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

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

Acylcarnitine analysis in blood and bile specimens to evaluate cases of sudden or unexpected death. Confirmatory enzymatic and molecular studies of cultured fibroblasts may be recommended.

Highlights

Analysis of acylcarnitines in blood and bile spots represents the first level of evaluation of a complete postmortem investigation of a sudden or unexpected death of an individual at any age.

 

Analysis facilitates the diagnosis of over 20 inborn errors of metabolism including fatty acid oxidation disorders and organic acidurias.

 

Abnormal results are not always sufficient to conclusively establish a diagnosis of a particular disease. When abnormal results are obtained, additional confirmatory testing is recommended.

 

Detailed reports for abnormal acylcarnitine profiles are provided that include an overview of the results and recommendations for follow-up.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Postmortem Screening Algorithm in Special Instructions.

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

Method Name
A short description of the method used to perform the test

Electrospray Tandem Mass Spectrometry (MS/MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Postmortem Screening

Aliases
Lists additional common names for a test, as an aid in searching

Blood Spots

FAO Disorder Screening

Fatty Acid Oxidation Disorder Screen

Metabolic Autopsy

SIDS Evaluation

Sudden Death Evaluation

Sudden Unexpected Death Evaluation

Unexpected Death Evaluation

SUDI

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Postmortem Screening Algorithm in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

Whole blood

Necessary Information

Request the original newborn screening card from the state laboratory where the decedent was born. See Request for Original Newborn Screening Card in Special Instructions.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Both bile and blood spots are required.

 

Supplies: Card-Postmortem Screening (Filter Paper) (T525)

Collection Container/Tube: Postmortem Screening Card

Specimen Volume: Properly completed screening card

Collection Instructions:

1. Collect blood in a heparin-containing tube and drop 25 mcL of blood onto the 2 circles labeled Blood.

2. Collect bile by direct puncture of the gallbladder and drop 25 mcL of bile onto the 2 circles labeled Bile.

3. Allow to dry at ambient temperature in a horizontal position for 3 or more hours.

4. Fill out information on page 2 of collection card.

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

6. Do not stack wet specimens.

7. Keep specimen dry.

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

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Bile spot: 1

Blood spot: 1

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Whole blood Ambient (preferred) FILTER PAPER
Frozen FILTER PAPER
Refrigerated FILTER PAPER

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

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

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

Acylcarnitine analysis in blood and bile specimens to evaluate cases of sudden or unexpected death. Confirmatory enzymatic and molecular studies of cultured fibroblasts may be recommended.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Postmortem Screening Algorithm in Special Instructions.

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

Postmortem screening involves acylcarnitine analysis in blood and bile specimens to evaluate cases of sudden or unexpected death. Acylcarnitine analysis can diagnose disorders of fatty acid oxidation and several organic acidurias, as relevant enzyme deficiencies cause the accumulation of specific acyl-CoAs measured by this assay. Fatty acid oxidation (FAO) plays a major role in energy production during periods of fasting. When the body's supply of glucose is depleted, fatty acids are mobilized from adipose tissue, taken up by the liver and muscles, and oxidized to acetyl-CoA. In the liver, acetyl-CoA is the building block for the synthesis of ketone bodies, which enter the blood stream and provide an alternative substrate for production of energy in other tissues when the supply of glucose is insufficient to maintain a normal level of energy. The acyl groups are conjugated with carnitine to form acylcarnitines, which are measured by tandem mass spectrometry (MS/MS). Diagnostic results are usually characterized by a pattern of significantly elevated acylcarnitine species compared to normal and disease controls.

 

In general, more than 20 inborn errors of metabolism can be identified using this method, including FAO disorders and organic acidurias. The major clinical manifestations associated with individual FAO disorders include hypoketotic hypoglycemia, variable degrees of liver disease and failure, skeletal myopathy, dilated/hypertrophic cardiomyopathy, and sudden or unexpected death. Organic acidurias also present as acute life-threatening events early in life with metabolic acidosis, increased anion gap, and neurologic distress. Patients with any of these disorders are at risk of developing fatal metabolic decompensations following the acquisition of even common infections. Once diagnosed, these disorders can be treated by avoidance of fasting, special diets, and cofactor and vitamin supplementation.

 

Analysis of acylcarnitines in blood and bile spots represents the first level of evaluation of a complete postmortem investigation of a sudden or unexpected death of an individual. Additional confirmatory testing is recommended. The diagnosis of an underlying FAO disorder or organic aciduria allows genetic counseling of the family, including the possible option of future prenatal diagnosis, and testing of at-risk family members of any age.

 

Disorders Detectable by Acylcarnitine Analysis*

Fatty Acid Oxidation Disorders:

-Short-chain acyl-CoA dehydrogenase (SCAD) deficiency

-Medium/Short-chain 3-hydroxyacyl-CoA dehydrogenase (M/SCHAD) deficiency

-Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

-Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency and trifunctional protein deficiency

-Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency

-Carnitine palmitoyl transferase type II (CPT-II) deficiency

-Carnitine-acylcarnitine translocase (CACT) deficiency

-Electron-Transferring Flavoproteins (ETF) deficiency, ETF-dehydrogenase deficiency (multiple acyl-CoA dehydrogenase deficiency: MADD; glutaric acidemia type II)

 

Organic Acid Disorders:

-Glutaryl-CoA dehydrogenase deficiency (glutaric acidemia type I)

-Propionic Acidemia

-Methylmalonic Acidemia

-Isovaleric Acidemia

-3-Hydroxy-3-methylglutaryl-CoA carboxylase deficiency

-3-Methylcrotonyl carboxylase deficiency

-Biotinidase deficiency

-Multiple carboxylase deficiency

-Isobutyryl-CoA dehydrogenase deficiency

-2-Methylbutyryl-CoA dehydrogenase deficiency

-Beta-ketothiolase deficiency

-Malonic aciduria

-Ethylmalonic encephalopathy 

*Further confirmatory testing is required for most of these conditions because an acylcarnitine profile can be suggestive of more than 1 condition.

 

See Postmortem Screening Algorithm in Special Instructions.

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.

Quantitative results are compared to a constantly updated range which corresponds to the 5 to 95 percentile interval of all postmortem cases analyzed in our laboratory.

Interpretation
Provides information to assist in interpretation of the test results

Reports of abnormal acylcarnitine profiles will include an overview of the results and of their significance, a correlation to available clinical information, possible differential diagnoses, recommendations for additional biochemical testing and confirmatory studies (enzyme assay, molecular analysis) as indicated, name and phone number of contacts who may provide these studies at Mayo Clinic or elsewhere, and a phone number to reach one of the laboratory directors in case the referring physician has additional questions.

 

Abnormal results are not always sufficient to conclusively establish a diagnosis of a particular disease. To verify a preliminary diagnosis based on an acylcarnitine analysis, independent biochemical (eg, FAO / Fatty Acid Oxidation Probe Assay, Fibroblast Culture) or molecular genetic analyses are required using additional tissue such as skin fibroblasts from the deceased patient. If not available, molecular genetic analysis of a patient's parents may enable the confirmation of a diagnosis.

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

Both blood and bile specimens must be collected in order to detect and independently confirm the largest possible number of disorders. However, if only 1 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.

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

1. Rinaldo P, Matern D, Bennet BJ: Fatty acid oxidation disorders. Ann Rev Physiol 2002;64:477-502

2. Rashed MS, Ozand PT, Bennett MJ, et al: Inborn errors of metabolism diagnosed in sudden death cases by acylcarnitine analysis of postmortem bile. Clin Chem 1995;41:1109-1114

3. Pryce JW, Weber MA, Heales S, et al: Tandem mass spectrometry findings at autopsy for detection of metabolic disease in infant deaths: postmortem changes and confounding factors. J Clin Pathol 2011;64:1005-1009. doi: 10.1136/jclinpath-2011-200218

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

Method Description
Describes how the test is performed and provides a method-specific reference

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)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Wednesday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

7 to 16 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

1 year

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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 US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83789

LOINC® Information

Test Id Test Order Name Order LOINC Value
PMSBB Postmortem Screening In Process
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip
22675 Specimen 31208-2
22676 Specimen ID 57723-9
22677 Source 31208-2
22678 Order Date 82785-7
22679 Reason For Referral 42349-1
22680 Method 85069-3
22684 Results In Process
81931 Interpretation 59462-2
22681 Amendment 48767-8
22682 Reviewed By 18771-6
22683 Release Date 82772-5

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports