Abstract
Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease caused by deficient activity of acid sphingomyelinase (ASM) enzyme, leading to the accumulation of varying degrees of sphingomyelin. Lipid storage leads to foam cell infiltration in tissues, and clinical features including hepatosplenomegaly, pulmonary insufficiency and in some cases central nervous system involvement. ASM enzyme replacement therapy is currently in clinical trial being the first treatment addressing the underlying pathology of the disease. Therefore, presently, it is critical to better comprehend ASMD to improve its diagnose and monitoring. Lung disease, including recurrent pulmonary infections, are common in ASMD patients. Along with lung disease, several immune system alterations have been described both in patients and in ASMD animal models, thus highlighting the role of ASM enzyme in the immune system. In this review, we summarized the pivotal roles of ASM in several immune system cells namely on macrophages, Natural Killer (NK) cells, NKT cells, B cells and T cells. In addition, an overview of diagnose, monitoring and treatment of ASMD is provided highlighting the new enzyme replacement therapy available.
Highlights
Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease (LSD)caused by deficient activity of the acid sphingomyelinase (ASM) enzyme, leading to the accumulation of sphingomyelin
The first sighting of ASMD was reported by Albert Niemann, in 1914, in an infant patient, but it was not until 1927 that the disease was considered clinically differentiated from Gaucher disease by Ludwig Pick, who reviewed reports of infants with rapidly progressive neurodegenerative disorders [1]
In patients with ASMD, the low levels of this enzyme lead to sphingomyelin accumulation and to the apparition of lipid laden cells designated as foam cells
Summary
Caused by deficient activity of the acid sphingomyelinase (ASM) enzyme, leading to the accumulation of sphingomyelin This disease is characterized by foam cell infiltration in different tissues, lipid storage and clinical manifestations which may overlap: pulmonary insufficiency, hepatosplenomegaly and neurodegeneration [1]. ASMD results from mutations on the SMPD1 gene (MIM# 607608), encoding for ASM The deficiency of this enzyme leads to accumulation of lipids, mainly sphingomyelin, in various tissues throughout the body, and this is responsible for the observed phenotypes. A is considered to be the direst form of ASMD, as it is fatal It is characterized by early infancy onset and little to no ASM residual activity, which leads to rapidly progressive systemic manifestation symptoms—mainly hepatosplenomegaly—and severe central nervous system impairment. We review the current knowledge on this disease, with a focus on the immunesystem alterations present and therapeutic approaches unfolding
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