CPT® Code 81251

Official Description

GBA (glucosidase, beta, acid) (eg, Gaucher disease) gene analysis, common variants (eg, N370S, 84GG, L444P, IVS2+1G>A)

Common Language Description

The CPT® Code 81251 pertains to the molecular genetic testing for the GBA (glucosidase, beta, acid) gene, which is crucial in diagnosing Gaucher disease. Gaucher disease is a type of lysosomal storage disorder that arises due to a deficiency of the enzyme glucocerebrosidase, which is essential for the breakdown of glucocerebroside, a lipid substance. When this enzyme is absent or deficient, glucocerebroside accumulates in various organs, including the liver, kidneys, spleen, bones, brain, and lungs, leading to a range of health complications. This condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene—one from each parent—to develop the disease. Those who inherit only one mutated copy become carriers and typically do not exhibit symptoms. The GBA gene has at least 25 known variants, with four common mutations: N370S, 84GG, L444P, and IVS2+1G>A. The specific combination of these variants can significantly affect the clinical presentation of Gaucher disease. For instance, individuals with the N370S/N370S genotype often experience non-neuropathic Type 1 Gaucher disease, which may present with mild or no symptoms. In contrast, combinations involving N370S with other variants can lead to more severe forms of the disease, such as Type 2 or Type 3, which are characterized by neurological involvement. The prevalence of Gaucher disease is notably higher among individuals of Ashkenazi Jewish descent, with a rate of approximately 1 in 450, compared to the general population, where the incidence is estimated at 1 in 50,000 to 100,000. Symptoms can vary widely and may include bone fractures, fatigue, heart valve issues, lung complications, skin discoloration, yellow fat deposits in the eyes, lymphadenopathy, joint swelling, painful bone lesions, thrombocytopenia, and severe edema in newborns. Treatment options include enzyme replacement therapy with intravenous glucocerebrosidase (imiglucerase) or velaglucerase alfa. Molecular genetic testing is recommended for individuals exhibiting symptoms of Gaucher disease or those with a family history of the condition, facilitating early diagnosis and management.

1. Indications

The molecular genetic testing for the GBA gene is indicated in specific clinical scenarios, particularly when there are symptoms or a family history suggestive of Gaucher disease. The following conditions warrant testing:

Symptoms of Gaucher Disease Individuals presenting with clinical manifestations associated with Gaucher disease, such as bone fractures, fatigue, heart valve problems, lung disease, skin discoloration, yellow fat deposits in the sclera, lymph node swelling, joint swelling, painful bone lesions, low platelet count, and severe edema in newborns, should undergo testing to confirm the diagnosis.
Family History Testing is also recommended for individuals with a known family history of Gaucher disease, as this genetic condition is inherited in an autosomal recessive pattern. Identifying carriers or affected individuals can aid in family planning and management.

2. Procedure

The procedure for molecular genetic testing of the GBA gene involves several key steps to ensure accurate identification of gene mutations. The following outlines the procedural steps:

Sample Collection A biological sample, typically blood or saliva, is collected from the individual undergoing testing. This sample serves as the source of DNA for analysis.
DNA Extraction The DNA is extracted from the collected sample using standardized laboratory techniques. This step is crucial for isolating the genetic material needed for testing.
Mutation Analysis The extracted DNA is then subjected to mutation analysis, focusing on the common variants of the GBA gene, including N370S, 84GG, L444P, and IVS2+1G>A. Advanced molecular techniques, such as polymerase chain reaction (PCR) and sequencing, are employed to detect these specific mutations.
Result Interpretation Once the analysis is complete, the results are interpreted by a qualified geneticist or laboratory specialist. They will determine whether any of the common variants are present and assess the implications for the individual’s health.
Reporting The findings are compiled into a comprehensive report, which is then communicated to the healthcare provider. This report includes details on the presence or absence of mutations, as well as any recommendations for further action or management based on the results.

3. Post-Procedure

After the molecular genetic testing for the GBA gene is completed, several considerations are important for both the patient and healthcare provider. The results may take several days to weeks to process, depending on the laboratory's workload and the complexity of the analysis. Once the results are available, it is essential for the healthcare provider to discuss the findings with the patient, including the implications of being a carrier or being diagnosed with Gaucher disease. If mutations are identified, the provider may recommend further evaluations, monitoring for symptoms, and potential treatment options, such as enzyme replacement therapy. Additionally, genetic counseling may be beneficial for the patient and their family to understand the hereditary nature of the disease, the risks of transmission to offspring, and the available support resources. Regular follow-up appointments may also be necessary to monitor the patient's health and manage any emerging symptoms associated with Gaucher disease.

Short Descr	GBA GENE
Medium Descr	GBA GLUCOSIDASE/BETA/ACID ANAL COMM VARIANTS
Long Descr	GBA (glucosidase, beta, acid) (eg, Gaucher disease) gene analysis, common variants (eg, N370S, 84GG, L444P, IVS2+1G>A)
Status Code	Statutory Exclusion (from MPFS, may be paid under other methodologies)
Global Days	XXX - Global Concept Does Not Apply
PC/TC Indicator (26, TC)	9 - Not Applicable
Multiple Procedures (51)	9 - Concept does not apply.
Bilateral Surgery (50)	9 - Concept does not apply.
Physician Supervisions	09 - Concept does not apply.
Assistant Surgeon (80, 82)	9 - Concept does not apply.
Co-Surgeons (62)	9 - Concept does not apply.
Team Surgery (66)	9 - Concept does not apply.
Diagnostic Imaging Family	99 - Concept Does Not Apply
CLIA Waived (QW)	No
APC Status Indicator	Service Paid under Fee Schedule or Payment System other than OPPS
Type of Service (TOS)	5 - Diagnostic Laboratory
Berenson-Eggers TOS (BETOS)	T1H - Lab tests - other (non-Medicare fee schedule)
MUE	1
CCS Clinical Classification	234 - Pathology

90	Reference (outside) laboratory: when laboratory procedures are performed by a party other than the treating or reporting physician or other qualified health care professional, the procedure may be identified by adding modifier 90 to the usual procedure number.
GW	Service not related to the hospice patient's terminal condition
59	Distinct procedural service: under certain circumstances, it may be necessary to indicate that a procedure or service was distinct or independent from other non-e/m services performed on the same day. modifier 59 is used to identify procedures/services, other than e/m services, that are not normally reported together, but are appropriate under the circumstances. documentation must support a different session, different procedure or surgery, different site or organ system, separate incision/excision, separate lesion, or separate injury (or area of injury in extensive injuries) not ordinarily encountered or performed on the same day by the same individual. however, when another already established modifier is appropriate it should be used rather than modifier 59. only if no more descriptive modifier is available, and the use of modifier 59 best explains the circumstances, should modifier 59 be used. note: modifier 59 should not be appended to an e/m service. to report a separate and distinct e/m service with a non-e/m service performed on the same date, see modifier 25.
GA	Waiver of liability statement issued as required by payer policy, individual case
XS	Separate structure, a service that is distinct because it was performed on a separate organ/structure
XU	Unusual non-overlapping service, the use of a service that is distinct because it does not overlap usual components of the main service