SUPERSEDED Local Coverage Determination (LCD)

MolDX: HLA-DQB1*06:02 Testing for Narcolepsy

L37003

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Superseded
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Document Note

Note History

Contractor Information

LCD Information

Document Information

Source LCD ID
N/A
LCD ID
L37003
Original ICD-9 LCD ID
Not Applicable
LCD Title
MolDX: HLA-DQB1*06:02 Testing for Narcolepsy
Proposed LCD in Comment Period
N/A
Source Proposed LCD
DL37003
Original Effective Date
For services performed on or after 07/17/2017
Revision Effective Date
For services performed on or after 07/08/2021
Revision Ending Date
06/28/2023
Retirement Date
N/A
Notice Period Start Date
06/01/2017
Notice Period End Date
07/16/2017
AMA CPT / ADA CDT / AHA NUBC Copyright Statement

CPT codes, descriptions and other data only are copyright 2023 American Medical Association. All Rights Reserved. Applicable FARS/HHSARS apply.

Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data contained or not contained herein.

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Copyright © 2023, the American Hospital Association, Chicago, Illinois. Reproduced with permission. No portion of the American Hospital Association (AHA) copyrighted materials contained within this publication may be copied without the express written consent of the AHA. AHA copyrighted materials including the UB‐04 codes and descriptions may not be removed, copied, or utilized within any software, product, service, solution or derivative work without the written consent of the AHA. If an entity wishes to utilize any AHA materials, please contact the AHA at 312‐893‐6816.

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Issue

Issue Description
Issue - Explanation of Change Between Proposed LCD and Final LCD

CMS National Coverage Policy

Title XVIII of the Social Security Act (SSA), §1862(a)(1)(A), states that no Medicare payment shall be made for items or services that “are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.”

CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, §80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests.

42 Code of Federal Regulations (CFR) §410.32 Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Coverage Guidance

Coverage Indications, Limitations, and/or Medical Necessity

Indications and Limitations of Coverage
Based upon currently available information, HLA-DQB1*06:02 typing (81383) for the diagnosis or management of narcolepsy is considered experimental/investigational/unproven for all populations. Although research suggests a strong association between HLA-DQB1*06:02 and narcolepsy risk, HLA-DQB1*06:02 typing is insufficient to confirm a diagnosis of narcolepsy, rule out a diagnosis of narcolepsy or quantify risk for narcolepsy. Therefore, at this time there is no clinical utility for genetic testing or HLA-DQB1*06:02 typing in the diagnosis or treatment of narcolepsy.

Background
Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy (sudden loss of voluntary muscle tone), and uncontrollable sleep episodes. Most cases of narcolepsy are sporadic, with symptoms beginning around the time of adolescence.

According to the International Classification of Sleep Disorders, Third Edition (ICSD-3) and the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-5), narcolepsy is diagnosed by a combination of physical exam, medical history, polysomnogram, multiple sleep latency testing (MSLT), and low CSF hypocretin-1 levels. Current recommended treatment options include stimulants and antidepressants. At this time, treatment is aimed towards the control of symptoms and is not curative.12

Narcolepsy has a multifactorial etiology, likely caused by the interaction between genetic risk factors and environmental exposures. Research efforts to identify the genetic contributors to narcolepsy have focused on an association between certain human leukocyte antigen (HLA) haplotypes and narcolepsy risk. The HLA complex encodes greater than 200 genes responsible for the recognition of foreign antigens. These genes are highly polymorphic, and certain alleles have long been known to confer risk for autoimmune disorders.

A variation of the HLA-DQB1 gene called HLA-DQB1*06:02 has been strongly associated with narcolepsy, particularly in individuals who also have cataplexy and a loss of hypocretins. Several genetic association studies in ethnically diverse populations have found a robust association between narcolepsy and the HLA-DQB1*06:02 allele. However, 15 to 25% of unaffected individuals in the general population also carry this risk haplotype, suggesting that it is necessary but not sufficient for the development of narcolepsy.6 Additionally, persons with narcolepsy and cataplexy have been identified without the HLA-DQB1*06:02 marker.4 More recent studies further suggest that predisposition to narcolepsy may be the result of complex genetic associations between multiple risk alleles.11

Despite multiple studies replicating the association between HLA-DQB1*06:02 and narcolepsy in different ethnic groups, the overall contribution of HLA variation to disease risk is low. Monozygotic twin studies have shown only partial concordance (25-31%), indicating that environmental factors play a large role in the etiology of narcolepsy.8 Recent studies have suggested that exposure to streptococcus, H1N1, and the H1N1 vaccine may also increase the risk for narcolepsy, specifically among individuals with the HLA-DQB1*06:02 allele.3,14,4

Although research suggests a strong association between HLA-DQB1*06:02 and narcolepsy risk, at this time there is no evidence for any diagnostic utility of HLA typing.5

Summary of Evidence

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Analysis of Evidence (Rationale for Determination)

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Proposed Process Information

Synopsis of Changes
Changes Fields Changed
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Associated Information
Sources of Information
Bibliography
Open Meetings
Meeting Date Meeting States Meeting Information
N/A
Contractor Advisory Committee (CAC) Meetings
Meeting Date Meeting States Meeting Information
N/A
MAC Meeting Information URLs
N/A
Proposed LCD Posting Date
Comment Period Start Date
Comment Period End Date
Reason for Proposed LCD
Requestor Information
This request was MAC initiated.
Requestor Name Requestor Letter
N/A
Contact for Comments on Proposed LCD

Coding Information

Bill Type Codes

Code Description
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Revenue Codes

Code Description
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CPT/HCPCS Codes

Group 1

Group 1 Paragraph

N/A

Group 1 Codes

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ICD-10-CM Codes that Support Medical Necessity

Group 1

Group 1 Paragraph:

N/A

Group 1 Codes:

N/A

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ICD-10-CM Codes that DO NOT Support Medical Necessity

Group 1

Group 1 Paragraph:

N/A

Group 1 Codes:

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Additional ICD-10 Information

General Information

Associated Information

N/A

Sources of Information
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Bibliography
  1. American Academy of Sleep Medicine. The International Classification of Sleep Disorders. 3rd ed. 2014.
  2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.
  3. Aran A, Lin L, Nevsimalova S, et al. Elevated anti-streptococcal antibodies in patients with recent narcolepsy onset. Sleep. 2009;32(8):979-983.
  4. Han F, Lin L, Schormair B, et al. HLA DQB1*06:02 negative narcolepsy with hypocretin/orexin deficiency. Sleep. 2014;37(10):1601-1608.
  5. Hong SC, Lin L, Jeong JH, et al. A study of the diagnostic utility of HLA typing, CSF hypocretin-1 measurements, and MSLT testing for the diagnosis of narcolepsy in 163 Korean patients with unexplained excessive daytime sleepiness. Sleep. 2006;29(11):1429-1438.
  6. Hor H, Kutalik Z, Dauvilliers Y, et al. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. Nature Genet. 2010;42(9):786-789.
  7. Lin L, Hungs M, Mignot E. Narcolepsy and the HLA region. J Neuroimmunol. 2001;117(1-2):9-20.
  8. Mignot E. Genetic and familial aspects of narcolepsy. Neurology. 1998;50(2 Suppl 1):S16-S22.
  9. Mignot E, Lin L, Rogers W, et al. Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. Am. J. Hum. Genet. 2001;68:686-699.
  10. Mignot E, Hayduk R, Black J, Grumet FC, Guilleminault C. HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients. Sleep. 1997;20(11):1012-1020.
  11. Miyagawa T, Toyoda H, Hirataka A, et al. New susceptibility variants to narcolepsy identified in HLA class II region. Hum Mol Genet. 2015;24(3):891-898.
  12. Morgenthaler TI, Kapur VK, Brown T, et al. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep. 2007;30(12):1705-1711.
  13. Online Mendelian Inheritance in Man (OMIM). #161400 Narcolepsy 1;NRCLP1. https://www.omim.org/entry/161400. Accessed May 17, 2021.
  14. Singh AK, Mahlios J, Mignot E. Genetic association, seasonal infections and autoimmune basis of narcolepsy. J Autoimmun. 2013;43:26-31.
  15. Tafti M, Hor H, Dauvilliers Y, et al. DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe. Sleep. 2014;37(1):19-25

Revision History Information

Revision History Date Revision History Number Revision History Explanation Reasons for Change
07/08/2021 R3

07/08/2021 Under CMS National Coverage Policy added regulation CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, §80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests. Under Sources of Information moved citations to bibliography. Under Bibliography changes were made to citations to reflect AMA citation guidelines. Review completed 05/18/2021.

  • Provider Education/Guidance
11/01/2019 R2

Change Request 10901 Local Coverage Determinations (LCDs): it will no longer be appropriate to include Current Procedure Terminology (CPT)/Health Care Procedure Coding System (HCPCS) codes or International Classification of Diseases Tenth Revision-Clinical Modification (ICD-10-CM) codes in the LCDs. All CPT/HCPCS, ICD-10 codes, and Billing and Coding Guidelines have been removed from this LCD and placed in the Billing and Coding Article related to this LCD. Consistent with Change Request 10901, if any language from IOMs and/or regulations was present in the LCD, it has been removed and the applicable manual/regulation has been referenced.

  • Other (compliance with CR 10901)
04/01/2018 R1

04/01/2018-Annual review completed 03/07/2018. At this time, 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Other (Annual Review)
N/A

Associated Documents

Attachments
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Related National Coverage Documents
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Public Versions
Updated On Effective Dates Status
08/23/2023 08/24/2023 - N/A Currently in Effect View
06/22/2023 06/29/2023 - 08/23/2023 Superseded View
06/29/2021 07/08/2021 - 06/28/2023 Superseded You are here
Some older versions have been archived. Please visit the MCD Archive Site to retrieve them.

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