Isovaleryl-CoA Dehydrogenase (IVD) Mutation Analysis (A282V)
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Confirmation of clinical and/or biochemical diagnosis of isovaleric acidemia
Providing prognostic information
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
This test includes only the A282V mutation. This mutation may confer a milder clinical phenotype. This test is recommended only after appropriate biochemical testing (OAU/80619 Organic Acids Screen, Urine).
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase Chain Reaction (PCR)-based assay (restriction enzyme digest) is used to detect the A282V mutation within exon 9 of the IVD gene.
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
IVD Mutation Analysis (A282V)
Isovaleric Acidemia (IVA)
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.
Specimen must arrive within 96 hours of draw.
Specimen Type: Whole blood
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
1. Invert several times to mix blood.
2. Send specimen in original tube.
1. Molecular Genetics-Biochemical Disorders Patient Information Sheet (Supply T527) in Special Instructions
2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
3. If not ordering electronically, submit a Molecular Genetics Request Form (Supply T245) 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.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine metabolism associated with germline mutations of the isovaleryl-CoA dehydrogenase gene. Mutations in this gene cause isovaleryl-CoA dehydrogenase (IVD) deficiency. This enzyme defect results in the accumulation of derivatives of isovaleryl-CoA, including free isovaleric acid, 3-OH valeric acid, N-isovalerylglycine, and isovalerylcarnitine. Diagnosis relies primarily on the identification of these metabolites in urine by organic acid and acylglycine analyses, and in plasma by acylcarnitine analysis.
Patients with IVA may present with various phenotypes, from the acute, neonatal phenotype to the chronic intermittent phenotype. Typically patients present with fairly non-specific features including poor feeding and vomiting. During these episodes, a characteristic smell of "dirty socks" may be present. In the past, many patients with neonatal onset died during the first episode, while survivors of acute manifestations often suffered neurological sequelae due to incurred central nervous system damage. Therefore, early diagnosis and treatment is of the utmost importance. Newborn screening for IVA was established to allow for early detection by acylcarnitine analysis and presymptomatic initiation of treatment. This early detection has led to improved prognosis for IVA patients.
Molecular follow up testing for patient's with positive newborn screening for IVA has led to the identification of specific mutant alleles. One such mutant allele, A282V, has been found to be over represented in patients detected by newborn screening. Clinical evaluation of patients with the A282V mutant allele suggests that this specific mutant allele may confer a milder clinical phenotype. Accordingly, determination of the patient's genotype with respect to the A282V mutation has implications for patient management and genetic counseling.
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.
An interpretive report will be provided.
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This assay will not detect all of the mutations that cause Isovaleric acidemia (IVA). Therefore, the absence of a detectable mutation(s) does not rule out the possibility that an individual is a carrier of or affected with this disease.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
In rare cases, DNA alterations of undetermined significance may be identified.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Many disorders may present with symptoms similar to those present in IVA. Therefore, biochemical assays (OAU/80619 Organic Acids Screen, Urine or ACYLG/81249 Acylglycines Quantitative, Urine) are recommended to establish the diagnosis of IVA prior to DNA analysis.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Ensenauer R, Vockley J, Grunert S, et al: A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric academia diagnosed by newborn screening. Am J Hum Genet 2004 Dec 75(6):1136-1142
2. Vockley J, Ensenauer R: Isovaleric acidemia: New aspects of genetic and phenotypic heterogeneity. Am J Med Genet 2006;42C:95-103
3. Sweetman L, Williams JC: Branched chain organic acidurias. In The Metabolic and Molecular Bases of Inherited Disease. Vol. 2. 8th edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, 2001, pp 2125-2163
Method Description Describes how the test is performed and provides a method-specific reference
A PCR-based assay is used to detect the A282V mutation within exon 9 of the isovaleryl-CoA dehydrogenase (IVD) IVD gene. Mutant and normal alleles are distinguished by digestion with the restriction enzyme BSA J1. (Hahn S: unpublished Mayo information)
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.
Tuesday; 2 p.m.
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
Whole Blood: 2 weeks (if available) Extracted DNA: 3 months
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.
81400-IVD (isovaleryl-CoA dehydrogenase) (eg, isovaleric acidemia), A28SV variant
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|
|22628||Reason For Referral||42349-1|