Test Catalog

Test Id : ALLOI

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Allo-isoleucine, Blood Spot

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Overview

Test Catalog

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

Evaluation of newborn screening specimens that test positive for branched-chain amino acids elevations

 

Follow-up of patients with maple syrup urine disease

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

Second-tier test for abnormal newborn screen and follow-up of patients with maple syrup urine disease.

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

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

Portions of this test are covered by patents held by Quest Diagnostics

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

Allo-isoleucine, BS

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

Branched-Chain Amino Acids (BCAA) Elevations

Newborn Screen

Newborn Screening

Maple Syrup Urine Disease (MSUD)

Maple Syrup Disease

Specimen Type
Describes the specimen type validated for testing

Whole blood

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

Supplies: Card - Blood Spot Collection (Filter Paper) (T493)

Container/Tube:

Preferred: Blood Spot Collection (Filter Paper)

Acceptable: Local newborn screening card, Whatman Protein Saver 903 filter paper, PerkinElmer 226filter paper, Munktell filter paper, Postmortem Screening Card

Specimen Volume: 2 Blood spots

Collection Instructions:

1. Do not use device or capillary tube containing EDTA to collect specimen.

2. At least 1 spot should be complete and unpunched.

3. 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.

4. Include type of feeding information on the collection card.

5. Let blood dry on filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.

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

7. Do not stack wet specimens.

8. Keep specimen dry.

Additional Information:

1. For collection instructions see Blood Spot Collection Instructions.

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

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

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

1 Blood spot

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

Blood spot shows layering
Serum rings
Multiple applications
Insufficient specimen 		Reject

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) 59 days FILTER PAPER
Frozen 59 days FILTER PAPER
Refrigerated 59 days FILTER PAPER

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

Evaluation of newborn screening specimens that test positive for branched-chain amino acids elevations

 

Follow-up of patients with maple syrup urine disease

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

Second-tier test for abnormal newborn screen and follow-up of patients with maple syrup urine disease.

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

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by the deficiency of the branched-chain-ketoacid dehydrogenase (BCKDH) complex. The BCKDH complex is involved in the metabolism of the branched-chain amino acids (BCAA) isoleucine (Ile), leucine (Leu), and valine (Val). Classic MSUD presents in the neonate with feeding intolerance, failure to thrive, vomiting, lethargy, and maple syrup odor to urine and cerumen. If untreated, it progresses to irreversible intellectual disability, hyperactivity, failure to thrive, seizures, coma, cerebral edema, and possibly death.

 

MSUD is a panethnic condition but is most prevalent in the Old Order Mennonite community in Lancaster, Pennsylvania with an incidence there of 1 in 760 live births. The incidence of MSUD is approximately 1 in 185,000 live births in the general population.

 

Newborn screening includes the measurement of BCAA (Leu, Ile, and Val), which are elevated in MSUD. However, unaffected infants receiving total parenteral nutrition frequently have increased levels of BCAA, a situation that often triggers unnecessary follow-up investigations. Abnormal concentrations of allo-isoleucine (Allo-Ile) are pathognomonic for MSUD. The determination of Allo-Ile (second-tier testing) in the same newborn screening specimens that reveal elevated BCAA allows for positive identification of patients with MSUD and differentiation from BCAA elevations due to dietary artifacts, reducing the occurrence of false-positive newborn screening results.

 

Treatment of MSUD aims to normalize the concentration of BCAA by dietary restriction of these amino acids. BCAA are essential amino acids, which require frequent adjustment of the dietary treatment. Dietary monitoring is accomplished by regular determination of BCAA and Allo-Ile concentrations.

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.

Allo-isoleucine: <2 nmol/mL

Leucine: 35-215 nmol/mL

Isoleucine: 13-130 nmol/mL

Valine: 51-325 nmol/mL

 

An interpretive report will also be provided.

Interpretation
Provides information to assist in interpretation of the test results

Allo-isoleucine is nearly undetectable in individuals not affected by maple syrup urine disease (MSUD). Accordingly, its presence is diagnostic for MSUD, and its absence is sufficient to rule-out MSUD.

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

No significant cautionary statements

Supportive Data

In a blinded study containing specimens obtained from maple syrup urine disease (MSUD) cases (n=16), non-MSUD patients treated with total parenteral nutrition (n=19), and healthy controls (n=541), this assay correctly identified all MSUD and non-MSUD cases.

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

1. Chace DH, Kalas TA, Naylor EW. Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns. Clin Chem. 2003;49(11):1797-1817. doi:10.1373/clinchem.2003.022178

2. Simon E, Fingerhut R, Baumkotter J, Konstantopoulou V, Ratschmann R, Wendel U. Maple syrup urine disease: Favorable effect of early diagnosis by newborn screening on the neonatal course of the disease. J Inherit Metab Dis. 2006;29(4):532-537. doi:10.1007/s10545-006-0315-y

3. Strauss KA, Puffenberger EG, Carson VJ. Maple syrup urine disease. In: Adam MP, Ardinger HH, Pagon RA, et al. eds. GeneReviews [Internet]. University of Washington, Seattle; 2006. Updated April 23, 2020. Accessed October 24, 2023. Available at www.ncbi.nlm.nih.gov/books/NBK1319/

4. Frazier DM, Allgeier C, Homer C, et al. Nutrition management guideline for maple syrup urine disease: An evidence- and consensus-based approach. Mol Genet Metab. 2014:112(3)210-217. doi:10.1016/j.ymgme.2014.05.006

5. Blackburn PR, Gass JM, Vairo FPE, et al. Maple syrup urine disease: mechanisms and management. Appl Clin Genet. 2017;10:57-66. doi:10.2147/TACG.S125962

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

This method quantifies valine (Val), allo-isoleucine (Allo-Ile), leucine (Ile), and leucine (Leu) using stable isotope-labeled internal standards (IS) d8-Val, d10-Allo-Ile, and d3-Leu. Branched-chain amino acids (BCAA) are extracted from a 3/16-inch dried blood spot (DBS) using a methanol:water (50:50) solution containing the IS. The filter plate containing the DBS and the IS are placed on an orbital shaker for 30 minutes at ambient temperature. The blood spot eluate is centrifuged into a 96-well round-bottom plate, dried under nitrogen, and reconstituted in aqueous mobile phase. BCAA are separated and detected by liquid chromatography tandem mass spectrometry in positive selected reaction monitoring mode.(Oglesbee D, Kramer K, Lacey J, et al. Second-tier test for quantification of alloisoleucine and branched-chain amino acids in dried blood spots to improve newborn screening of maple syrup urine disease [MSUD]. Clin Chem. 2008;54(3):542-549. doi:10.1373/clinchem.2007.098434; Stroek K, Boelen A, Bouva MJ, et al. Evaluation of 11 years of newborn screening for maple syrup urine disease in the Netherlands and a systematic review of the literature: Strategies for optimization. JIMD Rep. 2020;54(1):68-78. doi:10.1002/jmd2.12124)

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.

Monday through Friday

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.

2 to 4 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
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  • Prospective clients should contact their account representative. 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. It 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.

82136

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
ALLOI Allo-isoleucine, BS 94571-7
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
27457 Allo-isoleucine 94572-5
27458 Leucine 47679-6
27459 Isoleucine 47671-3
27460 Valine 47799-2
27453 Interpretation 46743-1
27455 Reviewed By 18771-6

Test Setup Resources

Setup Files
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Sample Reports
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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