CurrentAmbetter NevadaPolicy N/A

Genetic testing for nutrition and metabolism (G6PD, MTHFR, other metabolic disorders)

Defines medical necessity criteria for genetic testing related to nutrition and metabolism for members of Centene-affiliated health plans (Ambetter Nevada). Covers G6PD variant analysis, MTHFR variant analysis, and a list of other metabolic disorders with testing guidance.

Policy Summary

PayerAmbetter Nevada

PolicyGenetic testing for nutrition and metabolism (G6PD, MTHFR, other metabolic disorders)

Policy CodePolicy N/A

Change TypeNew policy / revised wording

Effective DateN/A

Next Review DateN/A

Key ActionOrder genetic testing to establish or confirm listed metabolic disorders only when the member demonstrates clinical features consistent with the disorder.

SourceLink

POLICY UPDATE CHANGES

New policy created with criteria incorporated from other policies and wording changed from 'investigational' to 'current evidence does not support…'.

3distinct testing topics

manyexamples listed

ACMGguideline cited

Coverage Criteria: Genetic Testing for Nutrition & Metabolism

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G6PD Variant Analysis: Current evidence does not support G6PD variant analysis to confirm or establish a diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency for all indications.

Diagnosis is typically achieved by quantitative spectrophotometric analysis or, more commonly, by a rapid fluorescent spot test detecting NADPH generation; molecular testing is available but not routine.

MTHFR Variant Analysis

Covered when ALL of the following are met:

MTHFR Variant Analysis: Current evidence does not support MTHFR targeted variant analysis (e.g., 677T, 1298C) for all indications, including but not limited to evaluation for thrombophilia, recurrent pregnancy loss, evaluation of at-risk relatives, or for drug metabolism/pharmacogenetic purposes.

ACMG practice guideline recommends against MTHFR polymorphism genotyping for thrombophilia, recurrent pregnancy loss, and for at-risk family members.

Other Covered Metabolic Disorders

Covered when ALL of the following are met:

Other Metabolic Disorders Testing: Genetic testing to establish or confirm one of the listed metabolic conditions to guide management is considered medically necessary when the member demonstrates clinical features consistent with the disorder.

Conditions include, but are not limited to: congenital adrenal hyperplasia (21-hydroxylase deficiency), congenital disorders of glycosylation, congenital hyperinsulinism; disorders of amino acid metabolism (GA-1, homocystinuria due to CBS deficiency, methylmalonic acidemia, propionic acidemia, MSUD); biotinidase deficiency; carnitine transport/cycle disorders (CPT II deficiency, primary carnitine deficiency); copper metabolism disorders (ATP7A-related disorders, Wilson disease); fatty acid oxidation disorders (MCAD); galactosemia; Glut1 DS; phenylalanine/tyrosine disorders (e.g., alkaptonuria, phenylalanine hydroxylase deficiency); porphyrin/heme disorders (acute intermittent porphyria); fibrous dysplasia/McCune-Albright; glycogen storage disorders (GSD I, Pompe); hypophosphatasia; Kallmann syndrome; lysosomal storage disorders (Gaucher, Krabbe, MPS I, MPS II, mucolipidosis IV); urea cycle disorders (OTC deficiency); malignant hyperthermia; and SHOX deficiency.

Unlisted Metabolic Disorders

Covered when ALL of the following are met:

Unlisted metabolic disorders: Genetic testing for metabolic disorders not specifically discussed within this policy will be evaluated according to the criteria outlined in the 'General Approach to Laboratory Testing' policy.

Clinical features for specific disorders may be referenced from GeneReviews, OMIM, Genetics Home Reference, or other scholarly sources when assessing medical necessity.

Current evidence does not support routine use of G6PD variant analysis or targeted MTHFR variant analysis to confirm or establish diagnoses for general indications. For G6PD, diagnosis is typically achieved by biochemical testing (quantitative spectrophotometric analysis or rapid fluorescent spot test) rather than routine molecular variant analysis. For MTHFR, targeted variant testing (e.g., 677T, 1298C) is not supported for routine indications including evaluation for thrombophilia, recurrent pregnancy loss, assessment of at-risk relatives, or routine pharmacogenetic/drug metabolism testing.

G6PD variant analysis and MTHFR polymorphism testing are specifically excluded from routine use because current evidence does not support their diagnostic utility for broad indications. For G6PD, biochemical assays (quantitative spectrophotometric or rapid fluorescent spot tests) are the standard diagnostic approaches and molecular testing is not routinely required to establish the diagnosis. For MTHFR, targeted variant analysis (e.g., 677T, 1298C) is not supported for common clinical scenarios such as thrombophilia evaluation, workup of recurrent pregnancy loss, testing of at-risk relatives, or routine pharmacogenetic purposes, per guideline-based recommendations.

When Genetic Testing Is Covered

Establish or confirm diagnosis of listed rare metabolic disorders to guide management when clinical features are present.

Covered when ANY of the following clinical-feature-driven indications apply:

Establish or confirm diagnosis of listed rare metabolic disorders to guide management: Genetic testing (single-gene testing, targeted panels, or appropriate molecular assays) to establish or confirm a diagnosis of a listed rare metabolic disorder is considered medically necessary when the member demonstrates clinical features consistent with the disorder.

Refer to disease-specific resources (e.g., GeneReviews, OMIM) for the characteristic clinical features used to justify testing.

Provider Requirements and Operational Notes

Prior Authorization

Prior Authorization and Code References

Prior Authorization Required: Specific genetic and diagnostic tests referenced in this policy (including G6PD enzyme assays and molecular/variant testing) are considered medically necessary only when the policy criteria are met and prior authorization is obtained when required by the plan.

Affected tests include G6PD enzyme assays, G6PD variant/molecular analysis, and other genetic tests used to establish or confirm metabolic disorders listed in the policy.
Providers must obtain prior authorization per Ambetter Nevada plan rules when required and document how submitted testing meets the medical necessity criteria in the policy.

Billing Rule

Coding Inclusion Is Not a Guarantee of Coverage

Coding inclusion is informational only. The presence of CPT/ICD codes in this policy does not guarantee coverage. Providers are responsible for verifying current coding guidance and benefit coverage prior to billing.

Review the most current CPT manuals and payer-specific coding resources before claim submission.
Check the Concert Platform or Ambetter Nevada provider resources for registered tests and applicable billing codes.

Documentation Required

G6PD Testing Pathway

Preferred diagnostic pathway for suspected G6PD deficiency: initial testing should generally use quantitative enzyme activity assays or rapid fluorescent spot tests (detecting NADPH generation). Molecular/variant analysis (G6PD variant analysis) is reserved as confirmatory or for specific clinical indications where enzyme testing is inconclusive or when detailed genotype information will impact management.

Obtain enzyme assay (quantitative spectrophotometric) or rapid fluorescent spot test first for diagnostic evaluation.
Reserve molecular/variant testing for confirmatory purposes, inconclusive enzyme results, atypical presentations, family studies, or when genotype affects treatment decisions.

Documentation Required

Clinical Features Required for Testing

Clinical features required for testing: genetic or diagnostic testing for G6PD deficiency and other metabolic disorders should be performed when the member demonstrates clinical signs/symptoms consistent with the disorder, or when testing is needed to guide management.

For G6PD deficiency consider testing with relevant hemolytic episodes, neonatal jaundice, family history, drug-induced hemolysis, or unexplained anemia.
For other metabolic disorders, test when clinical presentation, biochemical findings, or family history indicate the specific condition listed in the policy (e.g., congenital adrenal hyperplasia, congenital hyperinsulinism, amino acid metabolism disorders).
Document clinical features and rationale in the prior authorization request and medical record to support medical necessity.

Coding References

Referenced CPT CodesCPT

81247
81248
81249
81479
81291
81400
81401
81402
81403
81404

1–10 of 15

1/2

Referenced ICD-10 CodesICD-10

D55.0
E03.9
E55.9
E72.12
E78.2
E78.5
E88.9
N96
O03
R53.83

1–10 of 11

1/2

High myopia definition used in coding/clinical criteria.

DefinitionHigh myopia is defined as near-sightedness of -6.00 diopters or greater or an axial length greater than 26.5 mm.

Source organizationAmerican Association for Pediatric Ophthalmology & Strabismus (definition used in policy).

Coding relevanceUse this threshold when applying diagnosis or procedure coding that references high myopia in the policy.

Ordering Requirements

Note

Ordering requirements — test only when clinical features are present

Order testing to confirm or establish a diagnosis of a listed metabolic disorder only when the member demonstrates clinical features consistent with that disorder; follow the process outlined in the General Approach to Laboratory Testing as needed.

Testing should be targeted to conditions where the member's clinical presentation is consistent with the disorder.
Refer to the policy and the 'General Approach to Laboratory Testing' policy for ordering process details.

Frequency Limits and Retesting

G6PD enzyme activity (quantitative) — repeat testing guidance

Repeat testing guidanceIf an initial G6PD enzymatic (quantitative) test is negative during a hemolytic episode, repeat testing 3 months after resolution.

Test typeQuantitative test should report G6PD enzyme activity per gram of hemoglobin following positive screening.

Confirmatory methodsMolecular (DNA) confirmatory testing is available but not used routinely.

Not Covered / Experimental

Not covered: Routine G6PD variant analysis and routine targeted MTHFR polymorphism testing are not supported by current evidence for routine diagnostic indications. G6PD diagnosis should generally rely on biochemical enzyme testing, and MTHFR targeted variant analysis should not be used routinely for thrombophilia, recurrent pregnancy loss, evaluation of at-risk relatives, or for drug metabolism/pharmacogenetic testing.

Background

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is most commonly diagnosed with biochemical assays. Diagnosis can be achieved by quantitative spectrophotometric analysis or, more commonly in clinical practice, by a rapid fluorescent spot test that detects NADPH generation from NADP. While molecular confirmation via variant analysis is available, current evidence does not support routine use of molecular testing to establish the diagnosis for all indications.

Definitions

High myopia — definition used in the policy.

ThresholdNear-sightedness of -6.00 diopters or greater or axial length >26.5 mm.

Clinical useApplied as the policy definition of high myopia for diagnostic and coding decisions.

Reference noteDefinition taken from the American Association for Pediatric Ophthalmology & Strabismus as cited in the policy.

Marfanoid features — description referenced by the policy.

Core featuresPhysical features typically associated with Marfan Syndrome such as disproportionately tall, slender build; abnormally long/slender fingers and toes; and protruding or caving sternum.

Alternate wordingReferred to in policy as 'marfanoid features' or 'marfanoid habitus.'

Clinical implicationPresence of marfanoid features may be used to determine clinical appropriateness of testing referenced in the policy.

Revision History

2025-11-25policy_created

New policy created by incorporating criteria from prior policies (G6PD Variant Analysis from Concert Genetic Testing: Hematologic Conditions; MTHFR and Other Metabolic Disorders from MTHFR Variant Analysis) with references, rationale, background, and coding updated; wording changed from 'investigational' to 'current evidence does not support…'.

2025-12-25approvalLatest

Policy approved; reflects same substantive changes as 2025-11-25 creation entry (criteria incorporation and change in investigational wording to current evidence phrasing).

Policy Summary

PayerAmbetter Nevada

PolicyGenetic testing for nutrition and metabolism (G6PD, MTHFR, other metabolic disorders)

Policy CodePolicy N/A

Change TypeNew policy / revised wording

Effective DateN/A

Next Review DateN/A

Key ActionOrder genetic testing to establish or confirm listed metabolic disorders only when the member demonstrates clinical features consistent with the disorder.

SourceLink

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