Gaucher Disease
Gaucher Disease is the most common lysosomal storage disorder.
It is caused by autosomal recessive inheritance of mutations in the GBA gene that create deficiency of the enzyme glucocerebrosidase (also called beta-glucosidase).
PrintGaucher Disease is the most common lysosomal storage disorder.
It is caused by autosomal recessive inheritance of mutations in the GBA gene that create deficiency of the enzyme glucocerebrosidase (also called beta-glucosidase).
Gaucher Disease presents across a wide range of ages of onset and degrees of severity, with three major clinical types described. Genotype-phenotype correlation is not strictly reliable, though the common N370S mutation predisposes to type 1 disease and homozygous L444P mutations are strongly associated with neuronopathic types. Type 1 is non-neuronopathic; the central nervous system is spared. Disease types 2 and 3 are considered acute and subacute neuronopathic types, respectively.
Enzyme analysis is unsuitable for carrier testing due to the large overlap of carrier and non-carrier ranges. Full gene sequence analysis is useful for identification of uncommon alleles in affected individuals and for high-risk carrier testing, especially in non-Ashkenazi Jewish individuals. The Ambry Test: Gaucher Disease is a full gene sequence analysis with clinical sensitivity of approximately 99%.
Gaucher Disease is the most common lysosomal storage disorder. It is caused by autosomal recessive inheritance of mutations in the GBA gene that create deficiency of the enzyme glucocerebrosidase (also called beta-glucosidase) and accumulation of lipid in the lysosomes of various tissues.The disease presents across a wide range of ages of onset and degrees of severity, with three major clinical types described.
Type 1 disease includes enlargement of the spleen and liver; fractures, lesions, and pain in the bones; pulmonary hypertension and interstitial lung disease; and cytopenia. Type 1 is non-neuronopathic; the central nervous system is spared. It occurs most frequently in Ashkenazi Jewish individuals with an estimated incidence of 1/500 – 1/8001 and carrier frequency of 1/15.2,3 Incidence in the non-Ashkenazi is estimated to be 1/40,000 - 1/60,000.1 Type 1 typically affects adults but is extremely variable and includes children with significant organ disease as well as minimally affected or asymptomatic adults.4 Enzyme replacement therapy can reduce hepatosplenomegaly, bone loss, and anemia found in type 1 but cannot prevent the neurological disease found in the other types.3
Disease types 2 and 3 are considered acute and subacute neuronopathic types, respectively. They include symptoms of type 1 plus central nervous system dysfunction such as seizures, mental retardation, spasticity, and ataxia. Type 2 progresses rapidly from onset before age two to early childhood demise. Type 3 also has early onset but a slower course that may extend a few decades. Perinatal lethal and cardiovascular forms of Gaucher Disease have also been described.
Genotype-phenotype correlation is not strictly reliable, though the common N370S mutation predisposes to type 1 disease and homozygous L444P mutations are strongly associated with neuronopathic types.3
Diagnostic testing includes enzyme analysis, which is unsuitable for carrier testing due to the large overlap of carrier and non-carrier ranges.
Full gene sequence analysis is useful for identification of uncommon alleles in affected individuals and for high-risk carrier testing, especially in non-Ashkenazi Jewish individuals.
This Ambry Test is a full gene sequence analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 1-11 of the GBA gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns. Specific mutation analysis for individual GBA mutations known to be in the family is also available.
The Ambry Test: Gaucher Disease detects about 97% of all described GBA mutations (analytic sensitivity). As the undetected described mutations are very rare amongst affected patients, the clinical sensitivity is approximately 99%.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 μg in TE at 50-100 ng/μl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 1820 | GBA Gene Sequence Analysis | 83891x1, 83894x15, 83898x14, 83904x22, 83909x22, 83912x1 |
| Technique | Days |
|---|---|
| GBA Gene Sequence Analysis | 10-21 |
1 Weinreb NJ et al. Arch Intern Med. 2008;168:326-328.
2 Kronn D et al. Arch Intern Med. 1998;158:777-781.
3 Chen M and Wang J. Arch Pathol Lab Med. 2008;132:851-853.
4 Hruska KS et al. Hum Mutation. 2008;29:567-583.