Lysosomal Acid Lipase Deficiency: A Report of Two Cases and a Review of the Literature.

Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive genetic disease arising from mutations in the lipase A, lysosomal acid type (LIPA) gene, characterised by the formation of cholesterol esters and triglyceride storages, primarily in the liver and spleen. By analysing the level of lysosomal acid lipase (LAL), two forms were described in the literature: Wolman disease and cholesteryl-ester storage disease (CESD). Wolman disease usually manifests with rapidly progressive symptoms within the first year of life, while CESD is a latent condition, with significant features appearing later in life. LAL-D usually presents with a non-specific tableau, thus having the possibility of being incorrectly labelled. LAL activity can be demonstrated by LAL dried blood spot (DBS) testing. Since 2015, sebelipase alfa has been authorised for the treatment of LAL-D in the European Union, changing the course of this disease. This article aims to present two clinical cases of CESD and review the current literature on LAL-D. We presented two cases of CESD who were evaluated in our department for chronically elevated transaminases, one with and one without dyslipidaemia. For both patients, other causes of chronic hepatitis were excluded (viral infections, autoimmune diseases, and metabolic diseases), and LAL DBS testing was positive, establishing the diagnosis of CESD. One of them also underwent genetic testing, and a homozygous mutation of the LIPA gene was identified. LAL-D is a difficult diagnosis to establish, considering the scarcity of knowledge. In addition, neither the LAL DBS test nor LIPA gene sequencing investigations are largely available. Thus, most asymptomatic or minimally symptomatic patients might remain undiagnosed, and multiple complications without clear aetiology might arise, making this disease even harder to diagnose and manage. Nevertheless, even though the introduction of enzyme replacement therapy has improved outcomes for many patients, there still remains a need for increased awareness and understanding of this rare condition among health professionals.