In a liver workup, patients should be tested for LAL-D with an enzymatic blood test prior to biopsy. While the presence of microvesicular steatosis on biopsy may be suggestive of LAL-D, a liver biopsy is not recommended as a diagnostic procedure1.

* Doctor image is hypothetical

Treatment Options

Studies have summarized the observed effects of management options in LAL-D. The treatment of patients with LAL-D has been based on maintenance measures aimed at reducing the complications of the disease. Historical therapies have included low-fat diet, lipid-lowering medications, and transplant.6

Lipid-lowering Therapy

Lipid-lowering medications, including HMG-CoA reductase inhibitors commonly known as statins, are considered for management of LAL-D. Notably, LAL-D patients typically present with elevated serum LAL-D cholesterol, and in one study, 35 of 135 (26%) patients were treated with statins for hyperlipidemia. Of the 12 of 35 patients with LAL-D that continued taking statins with longitudinal data provided, liver disease was more advanced and progressed in all patients.3

Hematopoietic Stem cell Transplant (HSCT)

HSCT has been performed in infants with LAL-D, however it may not address the multisystemic nature of LAL-D. While information regarding long-term outcomes is limited, HSCT has been associated with serious complications.

Liver Transplantation

Often, patients experience liver failure caused by cirrhosis that has evolved as a consequence of acute or chronic conditions such as hepatitis A/B infections, glycogen storage disorders and LAL-D.2,6,7 Liver transplantation therefore represents a possible solution to imminent liver failure. While liver transplantation is a treatment currently available for patients with decompensated liver cirrhosis, transplant does not halt disease progression in LAL-D and complications due to heart, and kidney disease.3,6,8

Enzyme Replacement Therapy

The administration of an enzyme solution intended to substitute an absent or dysfunctional enzyme is considered enzyme replacement therapy (ERT). This type of therapy has been approved to treat various lysosomal storage diseases, including LAL-D. The primary ERT treatment for patients with LAL-D involves the use of recombinant human LAL. There is a risk for life-threatening and severe allergic reactions to the infusion of the therapy.1-3

1.   Reiner Z, Guardamagna O, and Nair D, et al. Lysosomal acid lipase deficiency--an under-recognized cause of dyslipidaemia and liver dysfunction. Atherosclerosis. 2014;235(1):21-30.
2.   Burton BK, Balwani M, and Feillet F, et al. A Phase 3 Trial of Sebelipase Alfa
in Lysosomal Acid Lipase Deficiency. N Engl J Med. 2015;373(11):1010-1020.
3.   Bernstein DL, Hülkova H, and Bialer MG, et al. Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol. 2013;58(6):1230-1243.
4.   Grundy SM, Brewer HB Jr, and Cleeman JI, et al. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004;109(3):433-438.
5.   Aguilar M, Bhuket T, and Torres S, et al. Prevalence of the metabolic syndrome in the United States, 2003-2012. JAMA. 2015;313(19):1973-1974.
6.   Rader DJ. Lysosomal Acid Lipase Deficiency--A New Therapy for a Genetic Lipid Disease. N Engl J Med. 2015;373(11):1071-1073.
7.   Keefe Emmet.  Hepatitis A and B Superimposed on Chronic Liver Disease: Vaccine-Preventable Diseases. Trans Am Clin Climatol Assoc.
8.   Bernstein DL, Lobritto S, and Lugaet A, et al. Lysosomal acid lipase deficiency allograft recurrence and liver failure- clinical outcomes of 18 liver transplantation patients. Mol Genet Metab. 2018;124(1):11-19