Test Id : HMGCR
3-Hydroxy-3-Methylglutaryl Coenzyme-A (HMG-CoA) Reductase, Serum
Useful For
Suggests clinical disorders or settings where the test may be helpful
Evaluating patients with suspected necrotizing autoimmune myopathy
Measuring 3-hydroxy-3-methylglutaryl-CoA reductase antibodies
Method Name
A short description of the method used to perform the test
Chemiluminescence Immunoassay (CIA)
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
HMGCR Ab
Necrotizing autoimmune myopathy (NAM)
NAM
Immune-mediated necrotizing myopathy
IMNM
Specimen Type
Describes the specimen type validated for testing
Serum
Ordering Guidance
NMS1 / Necrotizing Myopathy Evaluation, Serum is the preferred first tier test for identification of antibodies specific for necrotizing autoimmune myopathy (HMGCOA-IgG and SRP-IgG). This initial evaluation includes signal recognition particle (SRP) antibodies performed using tissue indirect immunofluorescence, which increases the clinical sensitivity as compared to SRP immunoblot methodologies.
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Collection Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 2 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
1 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
| Gross icterus | 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 |
|---|---|---|---|
| Serum | Refrigerated (preferred) | 28 days | |
| Ambient | 72 hours | ||
| Frozen | 28 days |
Useful For
Suggests clinical disorders or settings where the test may be helpful
Evaluating patients with suspected necrotizing autoimmune myopathy
Measuring 3-hydroxy-3-methylglutaryl-CoA reductase antibodies
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Necrotizing autoimmune myopathy (NAM) is a serious but rare muscle disease strongly associated with autoantibodies to either signal recognition protein (SRP) or 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR).(1) NAM typically manifests with subacute proximal limb muscle weakness and persistently elevated serum creatine kinase (CK) concentrations, but slower onset can occur and complicate diagnosis. Muscle biopsies in affected patients can demonstrate necrotic and regenerating myofibers without inflammatory infiltrates, suggesting the diagnosis.(2) However, sampling issues and lack of access to persons having expertise in obtaining, preparing, and interpreting muscle biopsy specimens may delay a diagnosis.(3)
Early identification of NAM and subsequent aggressive immune-modulating therapy is critical.(1,3) Discovery of SRP- or HMGCR-IgG autoantibodies can aid in establishing an earlier diagnosis and treatment initiation. In addition, the discovery of SRP or HMGCR autoantibodies should prompt a search for an underlying malignancy.(4) Serial testing for these autoantibodies can delay diagnosis with the discovery of either antibody aiding in establishing an earlier diagnosis and treatment initiation.(1,3)
The clinical onsets are not specific to NAM, consisting of proximal limb weakness in association with an elevated serum creatinine kinase, with or without exposure to lipid-lowering statin medications.(1,3-9) The clinical presentation can be confused with forms of inflammatory (dermatomyositis, polymyositis), toxic, metabolic, or even neurodegeneration (ie, muscular dystrophy) and the diagnosis delayed without serological testing by SRP- or HMGCR-autoantibody testing. Panel testing of both HMGCR and SRP autoantibodies is the preferred strategy for the best patient care.
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.
<20.0 CU
Interpretation
Provides information to assist in interpretation of the test results
Seropositivity for 3-hydroxy-3-methylglutaryl-CoA reductase autoantibodies supports the clinical diagnosis of necrotizing autoimmune myopathy (NAM). Confirmation with muscle biopsy is recommended. A paraneoplastic basis should be considered, according to age, sex, and other risk factors.(4) In cases of NAM, immune therapy is required and often multiple simultaneously utilized immunotherapies are needed to successfully treat patients.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Negative results do not exclude the diagnosis of necrotizing autoimmune myopathy (NAM). Only approximately 35% of cases of NAM are associated with autoantibodies against 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). The remainder of cases are either positive for signal recognition protein autoantibodies (approximately 20%-30%) or are seronegative (approximately 35%).
Very rarely HMGCR antibodies can be detected in diseases other than NAM. A muscle biopsy is recommended.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Kassardjian CD, Lennon VA, Alfugham NB, Mahler M, Milone M. Clinical features and treatment outcomes of necrotizing autoimmune myopathy. JAMA Neurol. 2015;72(9):996-1003
2. Emslie-Smith AM, Engel AG. Necrotizing myopathy with pipestem capillaries, microvascular deposition of the complement membrane attack complex (MAC), and minimal cellular infiltration. Neurology. 1991;41(6):936-939
3. Ramanathan S, Langguth D, Hardy T, et al. Clinical course and treatment of anti-HMGCR antibody-associated necrotizing autoimmune myopathy. Neurol Neuroimmunol Neuroinflamm. 2015;2(3):e96
4. Allenbach Y, Keraen J, Bouvier AM, et al. High risk of cancer in autoimmune necrotizing myopathies: usefulness of myositis specific antibody. Brain. 2016;139(Pt 8):2131-2135
5. Christopher-Stine L, Casciola-Rosen L, Hong G, Chung T, Corse AM, Mammen AL. A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum. 2010;62(9):2757-2766
6. Mammen AL, Chung T, Christopher-Stine L, et al. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum. 2011;63(3):713-721
7. Hengstman GJ, ter Laak HJ, Vree Egberts WT, et al. Anti-signal recognition particle autoantibodies: marker of a necrotising myopathy. Ann Rheum Dis. 2006;65(12):1635-1638
8. Miller T, Al-Lozi MT, Lopate G, Pestronk A. Myopathy with antibodies to the signal recognition particle: clinical and pathological features. J Neurol Neurosurg Psychiatry. 2002;73(4):420-428
9. Watanabe Y, Uruha A, Suzuki S, et al. Clinical features and prognosis in anti-SRP and anti-HMGCR necrotising myopathy. J Neurol Neurosurg Psychiatry. 2016;87(10):1038-1044
Method Description
Describes how the test is performed and provides a method-specific reference
IgG antibodies to 3-hydroxy-3- methylglutaryl coenzyme A reductase (HMGCR) are detected by a chemiluminescent assay using the Inova BIO-FLASH instrument. HMGCR antigen is coated on to paramagnetic beads, which are stored in the reagent cartridge lyophilized. When the assay cartridge is ready to be used for the first time, a buffer solution is added to the tube containing the beads, and the beads are resuspended with the buffer. The reagent cartridge is then loaded onto the BIO-FLASH instrument. A patient serum sample is diluted 1:17 by the instrument in a disposable plastic cuvette. An aliquot of the diluted patient serum, HMGCR-coupled beads, and assay buffer are combined into a second cuvette and mixed. This cuvette is incubated at 37 degrees C. The beads are then magnetized and washed several times. Isoluminol conjugated anti-human IgG antibody is then added to the cuvette and incubated at 37 degrees C. Again, the beads are magnetized and washed repeatedly. The isoluminol conjugate produces a luminescent reaction when "trigger" reagents are added to the cuvette. The light produced from this reaction is measured as relative light units (RLU) by the BIO-FLASH optical system. RLU values are proportional to the amount of bound isoluminol conjugate, which in turn is proportional to the amount of anti-HMGCR antibodies bound to the antigen on the beads. The QUANTA Flash HMGCR assay utilizes a predefined lot specific master curve that is uploaded into the instrument through the reagent cartridge barcode. Based on the results obtained by running two calibrators, an instrument specific working curve is created, which is used by the software to calculate chemiluminescent units from the RLU value obtained for each sample.(Package insert: QUANTA Flash HMGCR 701333. Inova Diagnostics, Inc; V04, 09/2018)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
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.
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
Indicates the location of the laboratory that performs the test
Fees :
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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 has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.
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.
CPT codes are provided by the performing laboratory.
82397
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 |
|---|---|---|
| HMGCR | HMG-CoA Reductase Ab, S | 93493-5 |
| 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.
|
|---|---|---|
| 607414 | HMG-CoA Reductase Ab, S | 93493-5 |