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Test ID: ALLOI Allo-isoleucine, Blood Spot

Reporting Name

Allo-isoleucine, BS

Useful For

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

 

Follow-up of patients with maple-syrup urine disease

Specimen Type

Whole blood


Specimen Required


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

Container/Tube: Local newborn 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 >1 year of age is fingerstick.

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

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

6. Do not stack wet specimens.

7. Keep specimen dry.

8. Let blood dry on the Blood Spot Collection Card (T493) at ambient temperature in a horizontal position for 3 hours before adding additional blood spots to the card.

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 spot: 1

Specimen Stability Information

Specimen Type Temperature Time
Whole blood Ambient (preferred)
  Frozen 
  Refrigerated 

Reference Values

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.

Day(s) and Time(s) Performed

Monday through Friday; 8 a.m.

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

82136

LOINC Code Information

Test ID Test Order Name Order LOINC Value
ALLOI Allo-isoleucine, BS In Process

 

Result ID Test Result Name Result LOINC Value
27446 Specimen 31208-2
27447 Specimen ID 57723-9
27448 Source 31208-2
27449 Order Date 82785-7
27450 Reason For Referral 42349-1
27451 Method 49549-9
27457 Allo-isoleucine 22670-4
27458 Leucine 20649-0
27459 Isoleucine 20648-2
27460 Valine 20661-5
27453 Interpretation 59462-2
27454 Amendment 48767-8
27455 Reviewed By In Process
27456 Release Date 82772-5

Clinical Information

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 mental retardation, hyperactivity, failure to thrive, seizures, coma, cerebral edema, and possibly death.

 

MSUD is a pan-ethnic condition, but is most prevalent in the Old Order Mennonite community in Lancaster, Pennsylvania with an incidence there of 1:760 live births. The incidence of MSUD is approximately 1:200,000 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 reveals 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. Because BCAA belong to the essential amino acids, the dietary treatment requires frequent adjustment, which is accomplished by regular determination of BCAA and Allo-Ile concentrations.

Interpretation

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.

Clinical Reference

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

2. Simon E, Fingerhut R, Baumkotter J, et al: Maple syrup urine disease: Favorable effect of early diagnosis by newborn screening on the neonatal course of the disease. J Inherit Metab Dis 2006;29:532-537

3. Morton DH, Strauss KA, Robinson DL, et al: Diagnosis and treatment of maple syrup disease: a study of 36 patients. Pediatrics 2002;109:999-1008

4. Oglesbee D, Sanders KA, Lacey JM, et al: Second-tier test for quantification of alloisoleucine and branched-chain amino acids in dried blood spots to improve newborn screening for maple syrup urine disease (MSUD). Clin Chem 2008 Mar;54(3):542-549

5. Strauss KA, Puffenberger EG, Morton DH: Maple Syrup Urine Disease. Updated 2013 May 9. Edited by RA Pagon, MP Adam, HH Ardinger. University of Washington, Seattle, 1993-2016. Available at www.ncbi.nlm.nih.gov/books/NBK1319

Analytic Time

2 days

Method Name

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Stable Isotope Dilution Analysis

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical