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DESCRIPTIONGenetic testing of adults with suspected lactase insufficiency is proposed as an alternative to current diagnostic practices, which include hydrogen breath test (HBT), lactose tolerance blood test (LTT), and intestinal biopsy. Studies have demonstrated a high correlation between a single nucleotide polymorphism (SNP), -13910 C>T upstream of the gene encoding the enzyme lactase, and lactase insufficiency in persons of European ancestry.
The predominant carbohydrate in milk is the disaccharide, lactose, consisting of the simple sugars glucose and galactose. The brush-border enzyme, lactase (also called lactase-phlorizin hydrolase), hydrolyzes lactose into its monosaccharide components, which are absorbable by the intestinal mucosa. Except for rare instances of congenital hypolactasia, most infants are able to produce lactase, and enzyme levels are highest at birth. Sometime after weaning in the majority of children, there is a decrease in lactase production through a multifactorial process that is regulated at the gene transcription level.
The decrease in lactase level varies significantly by ethnic group both in terms of the lowest level of lactase and time from weaning necessary to reach the nadir of lactase activity. By 2 to 12 years of age, two groups emerge: a group with insufficient levels of lactase activity (primary hypolactasia or lactase non-persistence) and a group that retains the infant level of lactase activity through adulthood (lactase-persistence).The ethnic groups with the highest rates of lactase insufficiency are Asian, Native American and African American, with the lowest rates in people of northern European origin.
Lactase insufficiency is a common condition which occurs in approximately (70%) of persons after weaning. An insufficiency of lactase results in the malabsorption of lactose, which may lead to symptoms of lactose intolerance such as abdominal pain, bloating, diarrhea and increased flatulence, caused by bacterial fermentation of undigested lactose in the colon. However, the demonstration of lactose malabsorption does not necessarily indicate that an individual will be symptomatic. Many variables determine if a person who malabsorbs lactose develops symptoms, including: the dose of lactose ingested, residual intestinal lactase activity, ingestion of food along with lactose, the ability of the colonic flora to ferment lactose and the individual sensitivity to the products of lactose fermentation. Because of these factors, the number of persons reporting symptoms of lactose intolerance is likely only a fraction of those who are lactase insufficient. In addition, lactose malabsorption may be secondary (secondary hypolactasia) to an acquired condition such as: small bowel bacterial overgrowth, infectious enteritis, mucosal damage from celiac disease, inflammatory bowel disease, antibiotics, gastrointestinal surgery, short bowel syndrome, radiation enteritis or other conditions which may lead to reduction of lactase expression in the small intestine.
Clinical Diagnosis of Lactase Insufficiency
Mucosal biopsy of the duodenum followed by biochemical lactase assay to directly measure lactase activity is the reference standard for diagnosis of lactase insufficiency. Although this approach may also exclude other causes of secondary lactose malabsorption, utility is limited due to the invasiveness of the procedure and the patchy expression of lactase in the duodenum.
Two common alternatives to this direct method of measuring lactase level are the hydrogen breath test (HBT) and lactose tolerance blood test (LTT) which measure lactose malabsorption. Because lactose malabsorption is nearly always attributable to lactase insufficiency, this can typically be imputed from measurements of lactose malabsorption.
The HBT measures the amount of hydrogen exhaled by gas chromatography for up to 3 hours after ingesting 25-50 g of lactose. Persons undergoing HBT are required to fast overnight and refrain from activities that may elevate breath hydrogen during testing. A rise in breath hydrogen of 0.31–2.5 mL/min is indicative of bacterial fermentation from the malabsorbed lactose. A negative HBT can exclude lactose malabsorption as the cause of symptoms, and a positive result indicates that the symptoms may be attributable to ingestion of lactose. The following factors are associated with a rise in breath hydrogen and may cause false-positive results if present at time of testing:
The LTT measures blood glucose increase over time with blood drawn at 15, 30, 60, and 90 minutes after ingesting a 25-50 g dose of lactose. A glucose increase of less than 20 mg/dL above an 8-hour fasting level indicates an abnormal test. The following factors are associated with a rise in blood sugar when undergoing a lactose tolerance test and may cause false-positive results:
Molecular Diagnosis of Lactase Insufficiency
Prometheus’s LactoType® is a commercially available PCR-based test that assesses the most common lactase non-persistence variant, MCM6 -13910 C>T, in patients with suspected lactose intolerance. Fulgent Clinical Diagnostics Lab also offers MCM6 sequencing and deletion/duplication analysis using next-generation sequencing. Demonstration of the C/C genotype can be used as indirect evidence of lactase insufficiency and lactose malabsorption.
Treatment of Lactase Insufficiency
No U.S. Food and Drug Administration (FDA)-cleared genotyping tests were found. Thus, genotyping is offered as a laboratory-developed test. Clinical laboratories may develop and validate tests in-house (“home-brew”) and market them as a laboratory service; such tests must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA). The laboratory offering the service must be licensed by CLIA for high-complexity testing.
POLICYThe use of targeted mutation analysis of -13910 C>T for the prediction of lactase insufficiency is considered investigational.
POLICY GUIDELINESInvestigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
07/18/2013: New policy added. Approved by Medical Policy Advisory Committee.
07/11/2014: Policy reviewed; description updated. Policy statement unchanged.
07/30/2015: Code Reference section updated for ICD-10.
09/14/2015: Policy description updated regarding tests. Policy statement unchanged. Investigative definition updated in the Policy Guidelines section.
SOURCE(S)Blue Cross and Blue Shield Association Policy # 2.04.94
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.