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

Dominik Soll, Dominik Spira, Tim Hollstein, Linus Haberbosch, Ilja Demuth, Elisabeth Steinhagen-Thiessen, Thomas Bobbert, Joachim Spranger, Ursula Kassner, Dominik Soll, Dominik Spira, Tim Hollstein, Linus Haberbosch, Ilja Demuth, Elisabeth Steinhagen-Thiessen, Thomas Bobbert, Joachim Spranger, Ursula Kassner

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).

Keywords: ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; Cholesteryl ester storage disease; HDL-C, High-density lipoprotein cholesterol; LAL, Lysosomal acid lipase; LALD registry; LALD, Lysosomal acid lipase deficiency; LDL-C, Low-density lipoprotein cholesterol; LIPA, Lysosomal acid lipase A; Lysosomal acid lipase deficiency (LALD); SA, Sebelipase alfa; Sebelipase alfa (Kanuma™).

Figures

Fig. 1
Fig. 1
Timeline of the patients' lipid profile (Total Cholesterol, HDL-C, LDL-C and Triglycerides in mg/dl). The initiation of the enzyme replacement treatment is marked by a dotted line and the term ‘Sebelipase alfa’.
Fig. 2
Fig. 2
Timeline of the patients' transaminases (in U/l) and total Bilirubin (in mg/dl). The initiation of the enzyme replacement treatment is again marked by a dotted line and the term ‘Sebelipase alfa’.

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