Local Coverage Determination (LCD)

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

L36464

Expand All | Collapse All
Proposed LCD
Proposed LCDs are works in progress that are available on the Medicare Coverage Database site for public review. Proposed LCDs are not necessarily a reflection of the current policies or practices of the contractor.

Document Note

Note History

Contractor Information

LCD Information

Document Information

Source LCD ID
N/A
LCD ID
L36464
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
DL36464
Original Effective Date
For services performed on or after 02/15/2016
Revision Effective Date
For services performed on or after 08/24/2023
Revision Ending Date
N/A
Retirement Date
N/A
Notice Period Start Date
01/19/2017
Notice Period End Date
03/05/2017

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.

Current Dental Terminology © 2023 American Dental Association. All rights reserved.

Copyright © 2024, the American Hospital Association, Chicago, Illinois. Reproduced with permission. No portion of the 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.

Making copies or utilizing the content of the UB‐04 Manual, including the codes and/or descriptions, for internal purposes, resale and/or to be used in any product or publication; creating any modified or derivative work of the UB‐04 Manual and/or codes and descriptions; and/or making any commercial use of UB‐04 Manual or any portion thereof, including the codes and/or descriptions, is only authorized with an express license from the American Hospital Association. The American Hospital Association (the "AHA") has not reviewed, and is not responsible for, the completeness or accuracy of any information contained in this material, nor was the AHA or any of its affiliates, involved in the preparation of this material, or the analysis of information provided in the material. The views and/or positions presented in the material do not necessarily represent the views of the AHA. CMS and its products and services are not endorsed by the AHA or any of its affiliates.

Issue

Issue Description

This LCD outlines noncoverage for this service with specific details under Coverage Indications, Limitations and/or Medical Necessity.

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, §80.1.1 Certification Changes

42 CFR §410.32(a) 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

N/A

Analysis of Evidence (Rationale for Determination)

N/A

Proposed Process Information

Synopsis of Changes
Changes Fields Changed
N/A
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
View Letter
N/A
Contact for Comments on Proposed LCD

Coding Information

Bill Type Codes

Code Description

Please accept the License to see the codes.

N/A

Revenue Codes

Code Description

Please accept the License to see the codes.

N/A

CPT/HCPCS Codes

Please accept the License to see the codes.

N/A

ICD-10-CM Codes that Support Medical Necessity

Group 1

Group 1 Paragraph:

N/A

Group 1 Codes:

N/A

N/A

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

Group 1

Group 1 Paragraph:

N/A

Group 1 Codes:

N/A

N/A

Additional ICD-10 Information

General Information

Associated Information
N/A
Sources of Information
N/A
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. doi:10.1093/sleep/32.8.979
  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. doi:10.5665/sleep.4066
  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. doi:10.1093/sleep/29.11.1429
  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. doi:10.1038/ng.647
  7. Lin L, Hungs M, Mignot E. Narcolepsy and the HLA region. J Neuroimmunol. 2001;117(1-2):9-20. doi:10.1016/s0165-5728(01)00333-2
  8. Mignot E. Genetic and familial aspects of narcolepsy. Neurology. 1998;50(2 Suppl 1):S16-S22. doi:10.1212/wnl.50.2_suppl_1.s16
  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. doi:10.1086/318799
  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. doi:10.1093/hmg/ddu480
  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. doi:10.1093/sleep/30.12.1705
  13. Online Mendelian Inheritance in Man (OMIM). #161400 Narcolepsy 1;NRCLP1. https://www.omim.org/entry/161400. Accessed July 5, 2023.
  14. Singh AK, Mahlios J, Mignot E. Genetic association, seasonal infections and autoimmune basis of narcolepsy. J Autoimmun. 2013;43:26-31. doi:10.1016/j.jaut.2013.02.003
  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. doi:10.5665/sleep.3300

Revision History Information

Revision History Date Revision History Number Revision History Explanation Reasons for Change
08/24/2023 R10

Under CMS National Coverage Policy updated section heading for 3rd regulation, and revised the following 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 to include section 80.1.1. Under Bibliography changes were made to citations to reflect AMA citation guidelines. 

  • Provider Education/Guidance
07/08/2021 R9

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.

  • Provider Education/Guidance
10/31/2019 R8

This LCD is being revised in order to adhere to CMS requirements per Chapter 13, Section 13.5.1 of the Program Integrity Manual, to remove all coding from LCDs. There has been no change in coverage with this LCD revision. Regulations regarding billing and coding were removed from the CMS National Coverage Policy section of this LCD and placed in the related Billing and Coding: MolDX: HLA-DQB1*06:02 Testing for Narcolepsy A56857 article.

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.

  • Provider Education/Guidance
08/15/2019 R7

All coding located in the Coding Information section has been moved into the related Billing and Coding: MolDX: HLA-DQB1*06:02 Testing for Narcolepsy A56857 article and removed from the LCD.

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.

  • Provider Education/Guidance
02/27/2018 R6

Removed the bold text formatting from the LCD title. There were no changes to the LCD coverage.

 

DATE (12/22/2017): 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.

 

 

  • Typographical Error
02/26/2018 R5 The Jurisdiction "J" Part B Contracts for Alabama (10112), Georgia (10212) and Tennessee (10312) are now being serviced by Palmetto GBA. The notice period for this LCD begins on 12/14/17 and ends on 02/25/18. Effective 02/26/18, these three contract numbers are being added to this LCD. No coverage, coding or other substantive changes (beyond the addition of the 3 Part B contract numbers) have been completed in this revision.
  • Change in Affiliated Contract Numbers
01/29/2018 R4 The Jurisdiction "J" Part A Contracts for Alabama (10111), Georgia (10211) and Tennessee (10311) are now being serviced by Palmetto GBA. The notice period for this LCD begins on 12/14/17 and ends on 01/28/18. Effective 01/29/18, these three contract numbers are being added to this LCD. No coverage, coding or other substantive changes (beyond the addition of the 3 Part A contract numbers) have been completed in this revision.
  • Change in Affiliated Contract Numbers
03/06/2017 R3 Release draft to final.
  • Other (Release draft to final.)
02/15/2016 R2 Annual review completed 12/22/2016, no changes.
  • Other (Annual review completed 12/22/2016, no changes.)
02/15/2016 R1 Moved ICD-10 Codes G47.411, G47.419 and G47.421 to the correct section. Deleted codes from ICD-10 Codes that Support Medical Necessity and added to ICD-10 Codes that DO NOT Support Medical Necessity section as stated in the indications.
  • Other (Moved ICD-10 Codes G47.411, G47.419 and G47.421 to the correct section.)
N/A

Associated Documents

Attachments
N/A
Related National Coverage Documents
N/A
Public Versions
Updated On Effective Dates Status
08/16/2023 08/24/2023 - N/A Currently in Effect You are here
Some older versions have been archived. Please visit the MCD Archive Site to retrieve them.

Keywords

N/A

Read the LCD Disclaimer