Wolman Disease and Cholesteryl Ester Storage Disease via the LIPA Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 7733 | LIPA | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Clinical Features
Wolman disease (WD, OMIM 278000) and cholesteryl ester storage disease (CESD, OMIM 278000) are rare storage disorders due to the deficiency of lysosomal acid lipase (LAL). This deficiency leads to the progressive accumulation of triglycerides and cholesteryl esters in the lysosomes of affected tissues (Patrick and Lake Nature 222:1067-1068, 1969). Although both WD and CESD present with divergent phenotypes, the two disorders can be distinguished on the basis of the age of onset, disease course, and severity. WD is characterized by onset of symptoms during the first or second month of life and death by the end of the first year from hepatic and adrenal failure. Typical symptoms include hepatosplenomegaly, steatorrhea, bilateral adrenal calcification, and failure to thrive (Dincsoy et al. Am J Clin Pathol 81:263-269, 1984). CESD is diagnosed within the first or second decade of life and follows milder course, with survival beyond middle age. Clinical features include hepatomegaly, hypercholesterolemia, and premature atherosclerosis (Burke and Schubert Science 176:309-310, 1972; Sloan and Fredrickson J Clin Invest 51:1923-1926, 1972). Biochemically, WD is characterized by a complete absence of LAL activity, while CESD patients maintain a residual enzyme activity.
Genetics
Wolman disease (WD) and cholesteryl ester storage disease (CESD) both exhibit autosomal recessive inheritance. Variants in the LIPA gene are responsible for LAL deficiency and subsequent development of both disorders (Anderson et al. Proc Natl Acad Sci USA 91:2718-2722, 1994; Klima et al. J Clin Invest 92:2713-2718, 1993). Worldwide, at least 15 variants have been reported in patients with CESD and 25 in patients with WD (http://www.hgmd.org/). Variants causing WD produce an enzyme with no activity or no enzyme at all, while at least one CESD mutant allele produces enough residual enzymatic function to ameliorate the phenotype (Anderson et al. Mol Genet Metab 68:333-345, 1999).
The LIPA gene encodes lysosomal acid lipase, which catalyzes the hydrolysis of cholestereyl esters and triglycerides.
Clinical Sensitivity - Sequencing with CNV PG-Select
Unknown at this time.
Testing Strategy
This test provides full coverage of all coding exons of the LIPA gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Patients with features suggestive of WD or CESD and their biological relatives are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LIPA.
Patients with features suggestive of WD or CESD and their biological relatives are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LIPA.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| LIPA | 613497 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Lysosomal Acid Lipase Deficiency | AR | 278000 |
Citations
- Anderson, R. A., et.al. (1994). "Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease." Proc Natl Acad Sci U S A 91(7): 2718-22. PubMed ID: 8146180
- Anderson, R. A., et.al. (1999). "Lysosomal acid lipase mutations that determine phenotype in Wolman and cholesterol ester storage disease." Mol Genet Metab 68(3): 333-45. PubMed ID: 10562460
- Burke, J. A., Schubert, W. K. (1972). "Deficient activity of hepatic acid lipase in cholesterol ester storage disease." Science 176(32): 309-10. PubMed ID: 5019788
- Dincsoy, H. P., et.al. (1984). "Cholesterol ester storage disease and mesenteric lipodystrophy." Am J Clin Pathol 81(2): 263-9. PubMed ID: 6198903
- Klima, H., et.al. (1993). "A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease." J Clin Invest 92(6): 2713-8. PubMed ID: 8254026
- Patrick, A. D., Lake, B. D. (1969). "Deficiency of an acid lipase in Wolman's disease." Nature 222(5198): 1067-8. PubMed ID: 5787090
- Sloan, H. R., Fredrickson, D. S. (1972). "Enzyme deficiency in cholesteryl ester storage idisease." J Clin Invest 51(7): 1923-6. PubMed ID: 5032533
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
Requisition Form
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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ORDER OPTIONS
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2) Select Additional Test Options
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