Clinical outcome of a patient with lysosomal acid lipase deficiency and first results after initiation of treatment with Sebelipase alfa: A case report

Abstract

We report on a case of very rare autosomal recessive cholesteryl ester storage disease due to lysosomal acid lipase deficiency (LALD). LALD is caused by mutations in the lysosomal acid lipase A ( LIPA ) gene resulting in cholesteryl ester accumulation in liver, spleen, and macrophages. It can lead to liver failure, accelerated atherosclerosis and premature death. Until recently, treatment options were limited to lipid-lowering medications to control dyslipidemia. Presently, a long-term enzyme replacement therapy with Sebelipase alfa, a recombinant human lysosomal acid lipase, is available for patients with LALD. Our patient's condition became conspicuous at the age of two due to a xanthogranuloma of the chin together with increased lipid levels, elevated liver enzymes and hepatomegaly. It took another five years until our patient was diagnosed with LALD after genetic testing. A bi-weekly therapy with intravenous Sebelipase alfa was started at the age of 26 years. It led to normalization of lipid levels, reduction of liver enzymes and beginning regression of hepatomegaly in the absence of adverse drug reactions after 46 infusions. Since LALD can take a fatal course even in patients with a long-term stable condition, it is essential to identify affected patients early and to treat them appropriately by enzyme replacement therapy. LALD should be suspected in patients with low high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C) in conjunction with elevated liver enzymes or hepatomegaly. A registry for LALD patients shall help to advance our understanding of the disease as well as improve patient care ( NCT01633489 ).

A Form of Metabolic-Associated Fatty Liver Disease Associated with a Novel LIPA Variant

“…21 Sebelipase alfa (Synageva BioPhar ma Corp., Lexington, MA, United States), a recombinant human LAL, is under development for use as enzymatic replacement therapy. The initial trial in adults showed a decrease in serum lipids and liver volume and normalization of liver transaminases, 22 and a phase 3 global trial is currently under way. 23 Timely diagnosis, as well as incorporation of LAL activity in newborn screening, will be needed to optimize the time to begin enzymatic replacement therapy.…”

Early Discovery of Children With Lysosomal Acid Lipase Deficiency With the Universal Familial Hypercholesterolemia Screening Program

“…International guidelines on the treatment of LAL-D are lacking. In 2012 (recruiting is still in progress), an international registry was started to improve the understanding of therapeutic interventions and their long-term effectiveness ( Soll et al, 2019 ).…”

The Association between Single Nucleotide Polymorphisms, including miR-499a Genetic Variants, and Dyslipidemia in Subjects Treated with Pharmacological or Phytochemical Lipid-Lowering Agents

“…As a potential miR-499 target, we identified the gene LIPA, which encodes for the lysosomal acid lipase (LAL), an enzyme responsible for the hydrolysis of triglycerides and cholesteryl esters (CE), resulting in the release of unesterified cholesterol and free fatty acids [ 48 ]. Mutations of LAL have been associated with CE and TG accumulation in the liver, spleen, and macrophages, resulting in liver failure, accelerated atherosclerosis, and premature death [ 49 ]. OSBPL1A, a member of the intracellular lipid receptors, was previously identified as a specific target of miR-499a-5p, and a reduced OSBPL1A activity was associated with a more pro-atherogenic lipid trait characterized by low plasma HDL-C levels [ 7 , 50 ].…”