Alpha-L-Iduronidase, Blood Spot
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Diagnosis of mucopolysaccharidosis I, Hurler, Scheie, and Hurler-Scheie syndromes using dried blood spot specimens
Fluorometric Enzyme Assay
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Preferred: Whatman Protein Saver 903 Paper
Acceptable: Ahlstrom 226 Filter Paper, Supplemental Newborn Screening Card (Supply T493)
Specimen Volume: 2 blood spots
1. An alternative blood collection option for a patient >1 year of age is fingerstick.
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry.
Additional Information: Provide a reason for referral with each specimen.
Forms: If not ordering electronically, submit a Biochemical Genetics Request Form (Supply T439) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Blood spot: 1
Blood spot specimen that shows serum rings or has multiple layers
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole blood||Ambient (preferred)||90 days|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The mucopolysaccharidoses are a group of lysosomal storage disorders caused by the deficiency of any of the enzymes involved in the stepwise degradation of dermatan sulfate, heparan sulfate, keratan sulfate, or chondroitin sulfate (glycosaminoglycans; GAG). Accumulation of GAG (previously called mucopolysaccharides; MPS) in lysosomes interferes with normal functioning of cells, tissues, and organs. There are 11 known disorders that involve the accumulation of GAG. MPS disorders involve multiple organ systems characterized by coarse facial features, cardiac abnormalities, organomegaly, intellectual disabilities, short stature and skeletal abnormalities.
Mucopolysaccharidosis I (MPS I) is an autosomal recessive disorder caused by a reduced or absent activity of the enzyme alpha-L-iduronidase due to mutations in the IDUA gene. More than 100 mutations have been reported in individuals with MPS I. Deficiency of alpha-L-iduronidase can result in a wide range of phenotypes categorized into 3 syndromes: Hurler syndrome (MPS IH), Scheie syndrome (MPS IS), and Hurler-Scheie syndrome (MPS IH/S). Because these syndromes cannot be distinguished biochemically, they are also referred to as MPS I and attenuated MPS I.
Clinical features and severity of symptoms of MPS I are variable, ranging from severe disease to an attenuated form that generally presents at a later onset with a milder clinical presentation. In general, symptoms may include coarse facies, progressive dysostosis multiplex, hepatosplenomegaly, corneal clouding, hearing loss, intellectual disabilities or learning difficulties, and cardiac valvular disease. The incidence of MPS I is approximately 1 in 100,000 live births. Treatment options include hematopoietic stem cell transplantation and enzyme replacement therapy.
A diagnostic workup in an individual with MPS I typically demonstrates elevated levels of urinary GAG (MPSQN/81473 Mucopolysaccharides [MPS], Quantitative, Urine) and increased amounts of both dermatan and heparan sulfate detected on thin-layer chromatography (MPSSC/84464 Mucopolysaccharides [MPS] Screen, Urine). Reduced or absent activity of alpha-L-iduronidase in blood spots, fibroblasts (IDST/8780 Alpha-L-Iduronidase, Fibroblasts), leukocytes, or whole blood (IDSWB/60618 Alpha-L-Iduronidase, Blood) can confirm a diagnosis of MPS I; however, enzymatic testing is not reliable for carrier detection. Molecular sequence analysis of the IDUA gene allows for detection of the disease-causing mutation in affected patients and subsequent carrier detection in relatives. To date, a clear genotype-phenotype correlation has not been established.
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.
> or =1.0 nmol/h/mL
An interpretive report will be provided.
Specimens with results <1.0 nmol/hour/mL in properly submitted specimens are consistent with alpha-L-iduronidase deficiency (mucopolysaccharidosis I). Further differentiation between Hurler, Scheie, and Hurler-Scheie is dependent on the clinical findings.
Normal results (> or =1.0 nmol/hour/mL) are not consistent with alpha-L-iduronidase deficiency.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The presence of a pseudodeficiency allele may cause reduced activity of alpha-L-iduronidase in the artificial substrate used in this assay. This can result in values below the normal reference range, but will typically be greater than levels found in patients with mucopolysaccharidosis I (MPS I).
This test cannot reliably determine carrier status for MPS I.
This test does not differentiate between Hurler and Scheie syndromes.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Neufeld EF, Muenzer J: The mucopolysaccharidoses. In The Metabolic and Molecular Basis of Inherited Disease. Vol 3. 8th edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. McGraw-Hill, Medical Publishing Division, 2001, p 3421
2. Chamoles NA, Blanco M, Gaggioli D, Casentini C: Hurler-like phenotype: enzymatic diagnosis in dried blood spots on filter paper. Clin Chem 2001;47:2098-2102
3. Martins AM, Dualibi AP, Norato D, et al: Guidelines for the management of mucopolysaccharidosis type I. J Pediatr 2009 Oct:155(4 Suppl):S32-S46
4. Enns GM, Steiner RD, Cowan TM: Lysosomal disorders: mucopolysaccharidoses. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth. McGraw-Hill, Medical Publishing Division, 2009, pp 721-730
5. Clarke LA, Heppner J: Mucopolysaccharidosis Type I. GeneReviews. Edited by RA Pagon, TD Bird, CR Dolan, et al. University of Washington, Seattle. Last updated July 2011
Method Description Describes how the test is performed and provides a method-specific reference
Whole blood is collected on grade 903 (Whatman) filter paper. A one-eighth inch (3-mm) disk is punched out of the dried blood spot (DBS) into a 96-well, round-bottom plate. Forty microliters of 50mM formate buffer with 0.3 micrograms D-saccharic acid-1,4-lactone is added as elution liquid and 20 microliters of 2 mM 4-methylumbelliferyl-alpha-L-iduronide in water as the substrate (60 microliters total volume + DBS). A blank is prepared using only elution liquid, substrate, and filter paper punches containing no blood (60 microliters total volume + blank punches). All patients, controls, and blank are set up in duplicate (2 punches total, 1 punch per well). After the incubation period (20 hours at 37 degrees C), all of the liquid from the plate is manually transferred to a 96-well, flat-bottom black plate. A calibration curve is prepared and analyzed on every plate to calculate enzyme activity results, based on fluorescence units in patient wells versus calibrators. The calibration is derived from 4-methylumbelliferone (4-MU) that is serially diluted manually in the plate with the highest calibrator being equivalent to an enzyme activity of 10.4 nmol/h/mL. Two hundred microliters of stop buffer (150 mM EDTA, pH 11.4) is added to all wells (patients, QC, blanks, calibrators). The plate is then read on the spectrofluorometer. Fluorescence readings for duplicate wells are averaged, and the average fluorescence is used to calculate the enzyme activity result. (Civallero G, Michelin K, de Mari J, et al: Twelve different enzyme assays on dried-blood filter paper samples for detection of patients with selected inherited lysosomal storage diseases. Clin Chim Acta 2006;372:98-102)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) 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 U.S. 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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|32352||Reason for Referral||42349-1|