SUPERSEDED Local Coverage Determination (LCD)

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

L36485

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Document Note

Note History

Contractor Information

LCD Information

Document Information

Source LCD ID
N/A
LCD ID
L36485
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
DL36485
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
09/18/2024
Retirement Date
N/A
Notice Period Start Date
01/19/2017
Notice Period End Date
03/05/2017

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Issue

Issue Description

Non-Coverage as outlined in coverage and limitations section.

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

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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
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Contractor Advisory Committee (CAC) Meetings
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Proposed LCD Posting Date
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Reason for Proposed LCD
Requestor Information
This request was MAC initiated.
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Contact for Comments on Proposed LCD

Coding Information

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CPT/HCPCS Codes

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ICD-10-CM Codes that Support Medical Necessity

Group 1

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Group 1 Codes:

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

Group 1

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Group 1 Codes:

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Additional ICD-10 Information

General Information

Associated Information
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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. 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 R13

R14

Revision Effective: 08/24/2023

Revision Explanation: 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 R12

R12

Revision Effective: 07/08/2021

Revision Explanation: 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.

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
12/24/2020 R11

R11

Revision Effective: 12/24/2020

Revision Explanation: Annual review no changes were made.

12/18/2020: 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)
12/26/2019 R10

R10

Revision Effective: 12/26/2019

Revision Explanation: Annual review no changes made.

12/20/2019: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)
10/31/2019 R9

R9

Revision Effective: 10/31/2019

Revision Explanation: Removed the following regulations from the CMS National policy section and placed in billing and coding article:

Title XVIII of the Social Security Act, §1833(e), prohibits Medicare payment for any claim lacking the necessary documentation to process the claim;

CMS Internet Online Manual Pub. 100-02 (Medicare Benefit Policy Manual), Chapter 15, Section 80, "Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests”;

CMS Internet-Only Manuals, Publication 100-04, Medicare Claims Processing Manual, Chapter 16, §50.5 Jurisdiction of Laboratory Claims, 60.1.2 Independent Laboratory Specimen Drawing, 60.2. Travel Allowance; and

CMS Internet Online Manual Pub. 100-04 (Medicare Claims Processing Manual), Chapter 23 (Section 10) "Reporting ICD Diagnosis and Procedure Codes”.

10/23/2019: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
09/19/2019 R8

R8

Revision Effective: 09/19/2019 Revision Explanation: Converted policy into new policy template that no longer includes coding section based on CR 10901. For Approval, no changes.

09/13/2019: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.

  • Revisions Due To Code Removal
09/19/2019 R7

R7

Revision Effective: 09/19/2019 Revision Explanation: Converted policy into new policy template that no longer includes coding section based on CR 10901.

09/12/2019: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.

  • Revisions Due To Code Removal
08/15/2019 R6

R6

Revision Effective: 08/15/2019

Revision Explanation: Based on CR 10901 instructions from CMS removed all coding from the policy and placed into a billing and coding articles that is related to the policy and can be found below.

08/08/2019-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 (Code Migration)
03/06/2017 R5

R5

Revision Effective: N/A

Revision Explanation: Annual review no changes made.

12/21/2018-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)
03/06/2017 R4

R4
Revision Effective: N/A
Revision Explanation: Annual review no changes made.

12/21/2017-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.

  • Other (annual review)
03/06/2017 R3 R3
Revision Effective: 03/06/2017
Revision Explanation: Released draft to final.
  • Provider Education/Guidance
02/15/2016 R2 R2
Revision Effective: N/A
Revision Explanation: Annual review no changes made.
  • Other (Annual Review)
02/15/2016 R1 R1
Revision Effective: 02/15/2016
Revision Explanation: Corrected ICd-10 from support medical necessity to does not support medical necessity.
  • Typographical Error
N/A

Associated Documents

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Public Versions
Updated On Effective Dates Status
09/14/2024 09/19/2024 - N/A Currently in Effect View
08/11/2023 08/24/2023 - 09/18/2024 Superseded You are here
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