Lysosomal acid lipase deficiency (LAL-D) is a genetic and progressive ultra-rare metabolic disease that leads to multi-organ damage and premature death.1

In patients with LAL-D, genetic mutations result in a marked decrease or loss of activity of the LAL enzyme—the enzyme responsible for the breakdown of cholesteryl esters and triglycerides.1 This deficiency leads to continuous accumulation of fatty material in the liver, spleen, gut, blood vessel walls and other tissue, resulting in progressive multi-organ damage including fibrosis, cirrhosis, liver failure, accelerated atherosclerosis, cardiovascular disease, and other devastating consequences.1,2

LAL-D threatens multiple vital organ systems, including the liver, heart, spleen and gastrointestinal tract.1 Liver manifestations are among the most common symptoms of LAL-D, and can include enlarged liver, fibrosis and/or cirrhosis, and liver failure.1,2 Patients with LAL-D are also likely to experience cardiovascular manifestations, including elevations in total cholesterol, triglycerides, and LDL-c, and decreased levels of HDL-c.2,5 Lipid metabolism abnormalities and the associated risk of accelerated atherosclerosis — the premature buildup of fats, cholesterol, and other substances in and on the artery walls — may contribute to premature mortality and morbidity in these patients.2

Infants with LAL-D face rapid disease progression in multiple organ systems that is typically fatal within a matter of months. In a study of 35 infants with LAL-D, 89% of patients (31/35) did not survive beyond one year of age and the median age of death was 3.7 months. In a subset of infants with early growth failure, 96% of patients (25/26) died within 1 year of birth and the median age of death was 3.5 months.3

In a study by Bernstein et al, the mean age of onset of LAL-D in paediatric and adult patients was 5.8 years; in another study by Burton et al., the mean age of onset was 9 years.1,4 Paediatric and adult patients also face substantial disease burden: in one study, 64.5% of paediatric and adult patients (20/31) with LAL-D with a clinical biopsy assessment showed evidence of fibrosis and/or cirrhosis. Eighty-five percent of these patients (17/20) were less than 18 years of age.4

Misdiagnosis is common among patients with LAL-D, leaving them at an increased risk for severe, unpredictable complications.1,2 Burton et al. noted a substantial difference between the mean age of onset (9 years) and the mean age at diagnosis (15.2 years), indicating that disease awareness and diagnostics need attention.4 LAL-D can be diagnosed with an enzymatic blood test.6

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1. Bernstein DL, et al. Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol. 2013;58:1230-43. doi:10.1016/j.jhep.2013.02.014.
2. Reiner Z, et al. Lysosomal acid lipase deficiency – an under-recognized cause of dyslipidemia and liver dysfunction. Atherosclerosis. 2014;235:21-30. doi:10.1016/j.atherosclerosis.2014.04.003.
3. Jones SA, et al. Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants. Genetics in Medicine. 27 August 2015. doi:10.1038/gim.2015.108
4. Burton BK, Deegan PB, Enns GM, et al. Clinical Features of Lysosomal Acid Lipase Deficiency. J Pediatr Gastroenterol Nutr. 2015;619-25. doi: 10.1097/MPG.0000000000000935.
5. Grabowski G. Lysosomal acid lipase deficiencies: the Wolman disease/cholesteryl ester storage disease spectrum [online]. In: Valle D, Beaudet AL, Vogelstein B, et al. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill; 2012.
6. Hamilton J, et al. A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin Chim Acta. 2012;413:1207-10. doi:10.1016/j.cca.2012.03.019.