[Acid sphingomyelinase deficiency: A review]

Abstract

Acid sphingomyelinase deficiency, formerly known as Niemann-Pick disease types B, A/B, and B, is a rare genetic disorder. It is an inherited autosomal recessive disease, linked to mutations in the SMPD1 gene. It is a lysosomal storage disease that leads to the accumulation of sphingomyelin mainly in macrophages, resulting in a multisystemic phenotype, primarily manifesting as hepatosplenomegaly and pulmonary involvement. The central nervous system may be affected, depending on the phenotype. Indeed, there is a phenotypic continuum among the three main forms that are distinguished: a chronic visceral form (formerly known as Niemann-Pick disease type B), a chronic neurovisceral form (intermediate form formerly known as Niemann-Pick disease type A/B), and an infantile neurovisceral form (formerly known as Niemann-Pick disease type A). The estimated overall prevalence is from 1 in 100,000 to 1 in 1,000,000 births. Clinical manifestations, as well as the age of onset of symptoms and/or diagnosis, vary depending on the form. The rarity of the disease and its nonspecific symptoms explain the diagnostic delay or failure to recognize the disease. Knowing and recognizing this disease is important, especially since there is an effective specific treatment through enzyme replacement therapy. In this article, we describe the clinical manifestations of acid sphingomyelinase deficiency, to understand when to suspect it, how to confirm it, and how to manage it.

Keywords: Acid sphingomyelinase deficiency; Déficit en sphingomyélinase acide; Lysosomal storage disease; Maladie de Niemann-Pick; Maladie lysosomale; Niemann-Pick disease; Olipudase alfa; Splenomegaly; Splénomégalie.