Test Id : RTQPC
Abnormal Prion Protein, Real-Time Quaking Induced Conversion, Spinal Fluid
Useful For
Suggests clinical disorders or settings where the test may be helpful
Aiding in diagnosing sporadic Creutzfeldt-Jakob disease or other prion disease in patients with a rapidly progressive dementia
Method Name
A short description of the method used to perform the test
Only orderable as part of a profile. For more information see:
CJDE / Creutzfeldt-Jakob Disease Evaluation, Spinal Fluid
RPDE / Rapidly Progressive Dementia Evaluation, Spinal Fluid
Real-Time Quaking-Induced Conversion (RT-QuIC)
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
Prion
CJD
Creutzfeldt Jakob Disease
Transmissible spongiform encephalopathies
RT-QuIC
Real-time quaking-induced conversion
TSE
Fatal Insomnia
Gerstmann-Straussler-Scheinker disease
Variant CJD
Seeding aggregation assay
PMCA
rpAD
Rapidly progressive AD
Rapidly progressive Alzheimer's disease
Specimen Type
Describes the specimen type validated for testing
CSF
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Only orderable as part of a profile. For more information see:
CJDE / Creutzfeldt-Jakob Disease Evaluation, Spinal Fluid
RPDE / Rapidly Progressive Dementia Evaluation, Spinal Fluid
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.
See Specimen Required
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 |
| Discolored CSF | 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 |
|---|---|---|---|
| CSF | Frozen (preferred) | 28 days | BlueTop SARSTEDT |
| Ambient | 12 hours | BlueTop SARSTEDT | |
| Refrigerated | 14 days | BlueTop SARSTEDT |
Useful For
Suggests clinical disorders or settings where the test may be helpful
Aiding in diagnosing sporadic Creutzfeldt-Jakob disease or other prion disease in patients with a rapidly progressive dementia
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
This evaluation is intended for use in patients with suspected Creutzfeldt-Jakob disease (CJD) and other human prion diseases. CJD is a rare and fatal neurodegenerative disorder that predominantly affects the brain and is caused by misfolded prion proteins (PrP[Sc]). CJD accounts for more than 90% of human prion diseases. Initial symptom onset is heterogenous but commonly includes rapidly progressive dementia, cerebellar ataxia, and myoclonus. The timeline of symptom progression and the pattern of symptom evolution can be divergent across patients and CJD subtypes, making an accurate diagnosis based on clinical presentation alone challenging. The inclusion of biomarkers with high diagnostic accuracy has improved the differentiation of CJD and related prion diseases from treatable neurological conditions with overlapping phenotypes. The real-time quaking-induced conversion (RT-QuIC) assay has been established to have strong clinical utility for early and accurate diagnosis of CJD through numerous independent studies in cerebrospinal fluid (CSF). Furthermore, the robustness and reproducibility of the RT-QuIC assay for CJD across laboratories has been demonstrated through international ring trials. The clinical sensitivity and specificity of second-generation RT-QuIC assays in CSF have been consistently reported to be greater than or equal to 92% and greater than or equal to 99%, respectively. Despite the high diagnostic accuracy of the assay, RT-QuIC results should be interpreted in the appropriate clinical context along with other clinical and paraclinical findings. A definitive diagnosis of sporadic prion disease can be established only through neuropathological assessment of brain tissue.
Unexpectedly negative RT-QuIC test results should prompt careful consideration of the differential diagnosis. If there is high suspicion of prion disease, repeat testing with RT-QuIC may be warranted. A small subset of cases initially negative by RT-QuIC may become positive as the disease progresses. However, RT-QuIC may be persistently negative in a small proportion of patients with definitive prion disease. False-negative RT-QuIC results are most often encountered in cases of genetic prion disease (eg, fatal familial insomnia and Gerstmann-Straussler-Scheinker disease) and in atypical sporadic prion disease subtypes (eg, MM2 cortical subtype) that have slower indolent disease progression. Other CSF biomarkers have been utilized to support the diagnosis of CJD, including 14-3-3, total Tau measurement, and the ratio of total Tau to phosphorylated Tau at threonine 181. Recent studies have indicated that the Tau ratio (total Tau to pT181-Tau or vice versa) has a very high diagnostic accuracy that exceeds that provided by total Tau or 14-3-3 enzyme-linked immunosorbent assays (ELISA). In a cohort of probable/definite CJD cases and controls tested utilizing the Roche Total-Tau and p-Tau (threonine 181) Elecsys assays, the optimized cut-off value for total Tau (>393 ng/L) had a clinical sensitivity and specificity of 92.3% and 88.3% for CJD, respectively, and the optimized cut-off value for the total Tau to p-Tau ratio (>18) has a clinical sensitivity and specificity of 97.4% and 95.9% for CJD, respectively.
Importantly, total Tau or total Tau to p-Tau ratios utilize assay-dependent cut-off values, and cut-off values from one assay are not transferable to different assay platforms.
The National Prion Disease Pathology Surveillance Center (NPDPSC) coordinates autopsies and neuropathologic examinations on suspected prion disease cases. More information about services available at the NPDPSC can be found at https://case.edu/medicine/pathology/divisions/prion-center.
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.
Only orderable as part of a profile. For more information see:
CJDE / Creutzfeldt-Jakob Disease Evaluation, Spinal Fluid
RPDE / Rapidly Progressive Dementia Evaluation, Spinal Fluid
Negative
Interpretation
Provides information to assist in interpretation of the test results
A positive real-time quaking-induced conversion (RT-QuIC) assay result is supportive of prion disease and, in the correct clinical context, fulfills the Centers of Disease Control and Prevention diagnostic criteria of probable prion disease.(1)
Negative results do not exclude the possibility of prion disease.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
These test results should be interpreted in the appropriate clinical context along with other clinical and paraclinical findings. Only through neuropathological assessment of brain tissue can a definitive diagnosis of sporadic prion disease be established.
Some molecular subtypes of prion protein have been reported to have lower detectability by real-time quaking-induced conversion (RT-QuIC).
Even small quantities of blood in CSF can result in false-negative RT-QuIC results.
The presence of fluorescent substances may interfere with testing and prevent an accurate interpretation of the RT-QuIC assay.
Careful consideration of the differential diagnosis is advised when RT-QuIC test results are unexpectedly negative. Repeat testing with RT-QuIC may be warranted if there is high suspicion of prion disease. A small subset of initially negative cases by RT-QuIC may become positive as the disease progresses. However, a small proportion of patients with definitive prion disease may be persistently negative by RT-QuIC. False-negative RT-QuIC results are most often encountered in cases of genetic prion disease, such as fatal familial insomnia and Gerstmann-Straussler-Scheinker disease, and in atypical sporadic prion disease subtypes that have slower indolent disease progression.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of High-Consequence Pathogens and Pathology (DHCPP). Diagnostic criteria: CDC's diagnostic criteria for Creutzfeldt-Jakob disease (CJD), 2018. CDC; Updated October 18, 2021. Accessed July 17, 2024. Available at www.cdc.gov/creutzfeldt-jakob/hcp/clinical-overview/diagnosis.html
2. Hermann P, Appleby B, Brandel JP, et al. Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. Lancet Neurol. 2021;20(3):235-46
3. Rhoads DD, Wrona A, Foutz A, et al. Diagnosis of prion diseases by RT-QuIC results in improved surveillance. Neurology. 2020;95(8):e1017-e1026
4. Hamlin C, Puoti G, Berri S, et al. A comparison of tau and 14-3-3 protein in the diagnosis of Creutzfeldt-Jakob disease. Neurology. 2012;79(6):547-552
5. Shir D, Lazar EB, Graff-Radford J, et al. Analysis of clinical features, diagnostic tests, and biomarkers in patients with suspected Creutzfeldt-Jakob disease, 2014-2021. JAMA Netw Open. 2022;5(8):e2225098
Method Description
Describes how the test is performed and provides a method-specific reference
This assay is a second-generation seeding aggregation assay known as a real-time quaking-induced conversion assay (RT-QuIC). Briefly, the cerebrospinal fluid sample is mixed with reaction buffer that contains fluorescence emitting dye and truncated recombinant hamster prion proteins (amino acids 90-231) in a 96-well black microtiter plate with clear optical bottom. Each 96-well plate includes 2 positive controls and 2 negative controls plus 20 samples. Each sample is tested in 4 replicate wells. At completion of the reaction, if at least one of the reaction wells per sample is scored positive, testing is repeated for that sample. The assay is performed on a BMG Omega FLUOStar instrument.(Orru CD, Groveman BR, Hughson AG, et al. RT-QuIC assays for prion disease detection and diagnostics. Methods Mol Biol. 2017;1658:185-203)
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, Tuesday, Thursday, Sunday
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 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.
CPT codes are provided by the performing laboratory.
84999
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 |
|---|---|---|
| RTQPC | RT-QuIC Prion, CSF | No LOINC Needed |
| 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.
|
|---|---|---|
| 620307 | RT-QuIC Prion, CSF | 101662-5 |