A Prospective, Cross-sectional Survey Study of the Natural History of Niemann-Pick Disease Type B

Abstract

Corresponding Author: Dr.

Types A and B Niemann-Pick disease

“…In contrast, type B patients have no overt signs of CNS involvement, but hepatosplenomegaly may be profound and accompanied by signs of liver failure [16][17][18]. Serum triglycerides and LDL-cholesterol are often elevated, while HDL-cholesterol is low.…”

“…Organomegaly can be significant, with an average splenic volume greater than ten multiples of normal [16][17][18]. Children with type B NPD often have growth restriction, particularly of linear growth, which is associated with a delayed bone age.…”

“…Almost one fifth of children with type B NPD died during the course of a longitudinal natural history study, suggesting that type B NPD is a serious, life-threatening pediatric disease. Detailed descriptions of the natural history and causes of morbidity and mortality in type B NPD have been published [e.g., 14,[16][17][18]28,29].…”

Morbidity and mortality in type B Niemann–Pick disease

“…10 Although there have been single case reports of deaths in patients with NP-B, to date there has been no systematic evaluation of the causes of mortality. In this article, we summarize the major morbidities in a series of 103 patients with NP-B who were evaluated at our center and describe the age and cause of death in 18 patients who died during the course of the study.…”

Novel first-dose adverse drug reactions during a phase I trial of olipudase alfa (recombinant human acid sphingomyelinase) in adults with Niemann–Pick disease type B (acid sphingomyelinase deficiency)

“…4 NPD encompasses a broad spectrum of clinical phenotypes, ranging from a neuronopathic form with severe somatic disease, failure to thrive, and death during early childhood (NPD A) to a nonneuronopathic form with survival usually into adulthood and variable degrees of hepatosplenomegaly, cytopenias, interstitial lung disease, and dyslipidemia (NPD B). [5][6][7][8] No definitive disease-modifying treatment is available for ASMD despite attempts to use splenectomy, pulmonary lavage, liver transplantation, and hematopoietic stem cell transplantation. [9][10][11][12][13] Preclinical studies in an ASM knockout mouse model of NPD demonstrated that biweekly administration of olipudase alfa reduced tissue sphingomyelin concentrations in a dosedependent manner.…”