• Test code: 06181
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Lysosomal Acid Lipase Deficiency Test

Test description

The Invitae Lysosomal Acid Lipase (LAL) Deficiency test analyzes LIPA, the gene that causes the accumulation of triglycerides, cholesterol esters and fats resulting in cholesteryl ester storage disease (CESD), a disorder with highly variable presentation and Wolman disease (WD), a serious infantile form of disease. This test is indicated for any individual in whom LAL deficiency is suspected based on clinical, radiologic, or laboratory findings. Identification of disease-causing variants provide accurate risk assessment and carrier status for at-risk relatives.

Order test

Primary panel (1 gene)
  • lysosomal acid lipase (LAL) deficiency
    • cholesteryl ester storage disease
    • Wolman disease

Clinical features of LAL deficiency include hepatomegaly, elevated serum transaminase, hypercholesterolemia, fatty liver disease, progressive liver fibrosis, and cirrhosis.

WD, an infantile form of LAL deficiency is characterized by acute infantile-onset symptoms including failure to thrive, hepatosplenomegaly, jaundice, diarrhea, vomiting, and anemia caused by hepatic accumulation of cholesterol esters and triglycerides.Adrenal gland calcifications result in adrenal cortical insufficiency. Untreated infants with classic WD do not survive beyond age one year. With recent FDA approval of enzyme replacement therapy for WD, the outlook for affected infants is improving.

CESD may manifest in childhood or later in life. The morbidity of late-onset CESD results from cardiovascular diseases, liver diseases, complications of secondary hypersplenism, and/or malabsorption. Individuals with CESD may have a normal life span depending on the severity of disease manifestations

Of individuals with a clinical diagnosis of LAL deficiency, >95% will have two pathogenic variants in LIPA.

LAL deficiency is inherited in an autosomal recessive pattern.

The prevalence of LAL deficiency has been estimated at 1 in 50,000 for CESD and 1 in 350,000 newborns for WD. Incidence is increased among the Iranian Jewish population and may be as high as 1:4200. This condition is panethnic and prevalence is likely underestimated because this is a rare and under-recognized condition.

Patients with higher elevation of ALT or AST, liver dysfunction, hepatomegaly, hepatic steatosis, non-alcoholic liver disease, and dyslipidemia.

  1. Muntoni, S, et al. Prevalence of cholesteryl ester storage disease. Arterioscler. Thromb. Vasc. Biol. 2007; 27(8):1866-8. PMID: 17634524
  2. Wierzbicka-Rucińska, A, et al. Diagnostic and therapeutic management of children with lysosomal acid lipase deficiency (LAL-D). Review of the literature and own experience. Dev Period Med. 2016; 20(3):212-215. PMID: 27941191
  3. Selvakumar, PK, et al. Reduced lysosomal acid lipase activity - A potential role in the pathogenesis of non alcoholic fatty liver disease in pediatric patients. Dig Liver Dis. 2016; 48(8):909-13. PMID: 27198736
  4. Baratta, F, et al. Reduced Lysosomal Acid Lipase Activity in Adult Patients With Non-alcoholic Fatty Liver Disease. EBioMedicine. 2015; 2(7):750-4. PMID: 26288848
  5. Valles-Ayoub, Y, et al. Wolman disease (LIPA p.G87V) genotype frequency in people of Iranian-Jewish ancestry. Genet Test Mol Biomarkers. 2011; 15(6):395-8. PMID: 21291321
  6. 2635281 PMID: 26352813
  7. Lohse, P, et al. Compound heterozygosity for a Wolman mutation is frequent among patients with cholesteryl ester storage disease. J. Lipid Res. 2000; 41(1):23-31. PMID: 10627498
  8. Pagani, F, et al. New lysosomal acid lipase gene mutants explain the phenotype of Wolman disease and cholesteryl ester storage disease. J. Lipid Res. 1998; 39(7):1382-8. PMID: 9684740
  9. Pisciotta, L, et al. Cholesteryl Ester Storage Disease (CESD) due to novel mutations in the LIPA gene. Mol. Genet. Metab. 2009; 97(2):143-8. PMID: 19307143
  10. Anderson, RA, et al. Lysosomal acid lipase mutations that determine phenotype in Wolman and cholesterol ester storage disease. Mol. Genet. Metab. 1999; 68(3):333-45. PMID: 10562460
  11. Lohse, P, et al. Molecular defects underlying Wolman disease appear to be more heterogeneous than those resulting in cholesteryl ester storage disease. J. Lipid Res. 1999; 40(2):221-8. PMID: 9925650
  12. Pagani, F, et al. Expression of lysosomal acid lipase mutants detected in three patients with cholesteryl ester storage disease. Hum. Mol. Genet. 1996; 5(10):1611-7. PMID: 8894696
  13. Aslanidis, C, et al. Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity. Genomics. 1996; 33(1):85-93. PMID: 8617513
  14. Fasano, T, et al. Lysosomal lipase deficiency: molecular characterization of eleven patients with Wolman or cholesteryl ester storage disease. Mol. Genet. Metab. 2012; 105(3):450-6. PMID: 22227072

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
LIPA NM_000235.3