Lysosomal Acid Lipase Deficiency: LIPA Gene Sequencing

Condition Description

Mutations in the LIPA gene (10q23.31) cause autosomal recessive lysosomal acid lipase deficiency.  The phenotype varies in clinical onset and the severity of the disease.  While lysosomal acid lipase deficiency is a spectrum, two distinct types have been described.  Wolman disease (WD) is on the severe end of the spectrum.  It is characterized by infantile onset, severe hepatosplenomegaly, failure to thrive, malabsorption, abdominal distention, steatorrhea, and adrenal calcification.  Cholesteryl esters and triglycerides are stored in the lysosomes of the small intestine, liver, and adrenal gland.  Plasma lipid levels are normal.  Cholesteryl ester storage disease (CESD) is on the milder end of the spectrum.  It is characterized by hepatomegaly, hypercholesterolemia, and deposition of cholesteryl esters in many tissues.  Premature atherosclerosis can develop in some patients.  

  • OMIM #613497: LIPA gene
  • OMIM #278000: Lysosomal acid lipase deficiency
  • Aslanidis et al. (1996). Genomics 33:85-93.
  • Du et al. (1998). Hum Mol Genet, 7:1347-1354.
  • Lee et al. (2011).  Mol Genet Genomics, 104:703-705.

Genes (1)


This test is indicated for:
  • Confirmation of a clinical diagnosis of lysosomal acid lipase deficiency.
  • Carrier testing in adults with a family history of lysosomal acid lipase deficiency.


PCR amplification of 9 exons contained in the LIPA gene is performed on the patient's genomic DNA. Direct sequencing of amplification products is performed in both forward and reverse directions, using automated fluorescence dideoxy sequencing methods. The patient's gene sequences are then compared to a normal reference sequence. Sequence variations are classified as mutations, benign variants unrelated to disease, or variations of unknown clinical significance. Variants of unknown clinical significance may require further studies of the patient and/or family members. This assay does not interrogate the promoter region, deep intronic regions, or other regulatory elements, and does not detect large deletions.


Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Analytical Sensitivity: ~99%

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with client services (
Submit only 1 of the following specimen types

Oragene™ Saliva Collection Kit
Orangene™ Saliva Collection Kit used according to manufacturer instructions. Please contact EGL for a Saliva Collection Kit for patients that cannot provide a blood sample.
Collection and Shipping
Please do not refrigerate or freeze saliva sample. Please store and ship at room temperature.
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.
  • Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
  • Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

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