Test ID: LALB    
Lysosomal Acid Lipase, Blood

Evaluation of patients with a clinical presentation suggestive of lysosomal acid lipase deficiency in blood specimens

This test is not useful to determine carrier status for cholesteryl ester storage disease (CESD) or Wolman disease (WD).

This test provides diagnostic testing for patients with clinical signs and symptoms suspicious for lysosomal acid lipase deficiency (LALD).

LALD is expressed phenotypically as infantile-onset Wolman disease (WD) or later-onset cholesterol ester storage disease (CESD).

Deficiency of lysosomal acid lipase (LAL) results in 2 clinically distinct phenotypes, Wolman disease (WD) and cholesteryl ester storage disease (CESD). Both phenotypes follow an autosomal recessive inheritance pattern and are caused by variant in the LIPA gene.

WD, the early-onset phenotype of LAL deficiency, is a lipid storage disorder characterized by vomiting, diarrhea, failure to thrive, abdominal distension, hepatosplenomegaly, and liver failure. Enlarged adrenal glands with calcification, a classic finding in WD, can lead to adrenal cortical insufficiency. Unless successfully treated, survival is rare beyond infancy.

CESD, the late-onset phenotype of LAL deficiency, is clinically variable with patients presenting at any age with progressive hepatomegaly and often splenomegaly, serum lipid abnormalities, and elevated liver enzymes. In childhood, patients can also present with failure to thrive and delayed milestones. Common features include premature atherosclerosis leading to coronary artery disease and strokes, liver disease of varying severity, and organomegaly. Lipid deposition in the intestinal tract can lead to diarrhea and weight loss.

CESD is likely underdiagnosed and frequently diagnosed incidentally after liver pathology reveals findings similar to nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). Birefringent cholesteryl ester crystals in hepatocytes or Kupffer cells in fresh-frozen tissues are visualized under polarized light and pathognomonic.

Enzyme replacement therapy (sebelipase alfa) was recently approved for both WD and CESD, and is now clinically available.

> or =21.0 nmol/hour/mL

Enzyme activity below 1.5 nmol/hour/mL in properly submitted samples is consistent with lysosomal acid lipase deficiency; Wolman disease or cholesteryl ester storage disease.

Normal results (> or =21.0 nmol/hour/mL) are not consistent with lysosomal acid lipase deficiency.

1. Bernstein DL, Hulkova H, Bialer MG, Desnick RJ: Cholesteryl ester storage disease: Review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol 2013;58:1230-1243

2. Reynolds T: Cholesteryl ester storage disease: a rare and possibly treatable cause of premature vascular disease and cirrhosis. J Clin Pathol 2013;66:918-923

3. Pericleous M, Kelly C, Wang T, et al: Wolman’s disease and cholesteryl ester storage disorder: the phenotypic spectrum of lysosomal acid lipase deficiency. Lancet Gastroenterol Hepatol 2017;2(9):670-679 doi:10.1016/S2468-1253(17)30052-3

• Informed Consent for Genetic Testing
• Biochemical Genetics Patient Information
• Informed Consent for Genetic Testing (Spanish)