CurrentBlue Cross Blue Shield - New MexicoPolicy CPCPLABO61

Testing for Alpha-1 Antitrypsin Deficiency

Laboratory reimbursement and coverage criteria for serum alpha-1 antitrypsin (AAT) quantification and AAT genotyping/phenotyping/proteotyping for Blue Cross Blue Shield of New Mexico members.

Policy Summary

PayerBlue Cross Blue Shield - New Mexico

PolicyTesting for Alpha-1 Antitrypsin Deficiency

Policy CodePolicy CPCPLABO61

Change TypeAdded lifetime frequency limitexpanded liver examplesadded neonatal cholestasis

Effective DateJan 3, 2026

Next Review DateN/A

Key ActionSubmit documentation supporting a listed reimbursable indication; testing is reimbursable once per lifetime when criteria are met.

SourceLink

POLICY UPDATE CHANGES

Added 'once per lifetime' limitation for reimbursable serum quantification and phenotyping/proteotyping in eligible situations.

Expanded examples in the liver disease indication to include chronic hepatitis with or without cirrhosis, chronically elevated aminotransferase levels, portal hypertension, primary liver cancer.

Neonatal cholestasis was added as an explicitly reimbursable indication.

Specified that phenotyping/proteotyping for Z and S alleles should be performed using LC-MS/MS and that phenotyping uses isoelectric focusing.

once per lifetimefrequency limit

1.0policy version

2025-09-26policy approval

2026-01-03

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria for AAT Testing

Reimbursable Indications (Initial testing)

Covered when ALL of the following are met: serum AAT quantification and phenotyping/proteotyping may be reimbursed once per lifetime in any of these situations.

Eligible clinical indications: a) Symptomatic individuals 18 years of age or older with emphysema, COPD, or asthma; b) Individuals with unexplained liver disease (examples: chronic hepatitis with or without cirrhosis, chronically elevated aminotransferase levels, portal hypertension, primary liver cancer); c) Individuals with persistent obstruction on pulmonary function tests without identifiable risk factors (e.g., cigarette smoking, occupational exposure); d) Individuals 18 years of age or older with necrotizing panniculitis; e) Siblings of an individual with known alpha-1 antitrypsin (AAT) deficiency; f) Individuals with anti-proteinase 3-positive vasculitis (C-ANCA positive); g) Individuals with bronchiectasis without evident etiology; h) Individuals with neonatal cholestasis.once per lifetime

Phenotyping/proteotyping methods: isoelectric focusing for phenotyping; LC-MS/MS for proteotyping of Z and S alleles.

Phenotyping for discordant or negative genotype

Covered when ALL of the following are met:

Additional phenotyping indication: For individuals who have negative genotype results for common variants or who have discordant results between AAT serum levels and proteotype, but for whom clinical suspicion of AAT deficiency remains, isoelectric focusing/phenotyping may be reimbursable.

Phenotyping should be performed using isoelectric focusing; proteotyping for Z and S alleles should be performed using LC-MS/MS (see Note 1).

Testing for alpha-1 antitrypsin (AAT) deficiency is not reimbursable when the clinical situation does not meet one of the explicitly listed reimbursable indications. The policy specifies that serum AAT quantification and AAT phenotyping/proteotyping are eligible for reimbursement once per lifetime only in the defined situations (see Reimbursable Indications). Any request for testing outside those situations should be considered non‑reimbursable.

Any testing performed for indications that are not among the listed eligible indications is considered not reimbursable. Claims for AAT serum quantification, genotyping, phenotyping, or proteotyping submitted for other clinical reasons may be denied under this policy.

List of Covered Indications

Symptomatic adults (>=18) with emphysema, COPD, or asthma

Eligibility: Symptomatic individuals 18 years of age or older with emphysema, COPD, or asthma.

Unexplained liver disease (examples: chronic hepatitis +/- cirrhosis, elevated aminotransferases, portal hypertension, primary liver cancer)

Eligibility: Individuals with unexplained liver disease (examples include chronic hepatitis with or without cirrhosis, chronically elevated aminotransferase levels, portal hypertension, primary liver cancer).

Persistent obstruction on PFTs without identifiable risk factors

Eligibility: Individuals with persistent obstruction on pulmonary function tests without identifiable risk factors (e.g., cigarette smoking, occupational exposure).

Procedure Codes and Frequency Limits

Procedure Codes (not exhaustive)mixed

No codes listed

Frequency limit — once per lifetime

LimitOnce per lifetime for reimbursable serum AAT quantification and AAT phenotyping/proteotyping when criteria are met

Applies toSerum alpha-1 antitrypsin (AAT) quantification and AAT phenotyping or proteotyping (see Note 1)

ScopeOnly applies when one of the listed reimbursable clinical indications is documented

Frequency Limits for Reimbursable Testing

Serum AAT quantification and phenotyping/proteotyping when reimbursable — once per lifetime

Reimbursable testsSerum AAT quantification and AAT phenotyping or AAT proteotyping may be reimbursed once per lifetime when criteria are met

Eligible situationsIncludes symptomatic adults with emphysema/COPD/asthma; unexplained liver disease (examples listed); persistent PFT obstruction without risk factors; necrotizing panniculitis; siblings of affected individuals; bronchiectasis without etiology; C-ANCA–positive vasculitis; neonatal cholestasis

ExceptionPhenotyping may be reimbursable for discordant or negative genotype results with ongoing clinical suspicion

Provider Actions and Documentation Requirements

Prior Authorization

No explicit prior authorization requirement is stated in this policy. Providers should review member-specific plan documents and product-specific coverage documents to determine whether prior authorization is required for testing in a given case.

Note

Provider Billing and Coding Responsibilities

Providers must follow plan and contract requirements and submit claims using appropriate, industry-standard coding (CPT, HCPCS, ICD-10, NDC, revenue codes) and billing conventions. Claims are subject to code edit protocols and claim review; providers may be asked to supply additional documentation upon request.

Documentation Required

Clinical Documentation Required

Clinical documentation must be submitted to support one of the reimbursable indications listed in this policy. Documentation should include relevant clinical notes, test results (e.g., serum AAT level, genotype/proteotype results, isoelectric focusing when performed), and evidence of symptoms or diagnoses that meet the covered indications (for example, emphysema/COPD, unexplained liver disease, necrotizing panniculitis, neonatal cholestasis, bronchiectasis, C-ANCA–positive vasculitis, or affected sibling).

Ordering and Authorization Notes

Note

Ordering requirements — verify product-specific rules

Not all ordering, coverage, or authorization requirements in this policy apply to every BCBSNM product; review the member’s specific plan documents to confirm product‑specific coverage, ordering rules, and any authorization requirements before ordering testing.

Definitions and Testing Methods

AAT phenotyping (isoelectric focusing)

DefinitionAAT phenotyping: laboratory method performed using isoelectric focusing to determine AAT protein variants

PurposeUsed to characterize AAT protein variants when genotype or serum level results are discordant or additional characterization is needed

Reference noteSee Note 1 in policy for preferred methodology

AAT proteotyping / Pi-typing (LC-MS/MS)

DefinitionAAT proteotyping (Pi-typing): protease inhibitor typing for Z and S alleles performed using liquid chromatography–tandem mass spectrometry (LC-MS/MS)

Target allelesSpecifically identifies Z and S AAT alleles via LC-MS/MS proteotype analysis

Background

Alpha-1 antitrypsin (AAT) deficiency is an inherited disorder in which insufficient or dysfunctional AAT protein increases risk for pulmonary and hepatic disease. Clinically, AAT deficiency is associated with early‑onset emphysema/COPD and may present with chronic liver disease including cirrhosis and primary liver cancer. Other recognized manifestations include necrotizing panniculitis, bronchiectasis without an evident cause, certain vasculitides (for example, C-ANCA–positive disease), and neonatal cholestasis. Laboratory evaluation commonly includes serum AAT quantification and targeted genotype or protein‑based phenotyping/proteotyping when clinically indicated.

Not Covered

Testing for AAT deficiency for any indication other than those explicitly listed in the Reimbursable Indications section is not reimbursable. Providers should confirm that the patient’s presentation matches one of the policy’s eligible clinical indications before ordering tests to avoid claim denials.