Types A and B Niemann-Pick disease

Abstract

The eponym Niemann-Pick disease (NPD) refers to a group of patients who present with varying degrees of lipid storage and foam cell infiltration in tissues, as well as overlapping clinical features including hepatosplenomegaly, pulmonary insufficiency and/or central nervous system (CNS) involvement. Due to the pioneering work of Roscoe Brady and co-workers, we now know that there are two distinct metabolic abnormalities that account for NPD. The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM; “types A & B” NPD), and the second is due to defective function in cholesterol transport (“type C” NPD). Herein only types A and B NPD will be discussed. Type A NPD patients exhibit hepatosplenomegaly in infancy and profound CNS involvement. They rarely survive beyond 2–3 years of age. Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no CNS signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Intermediate patients also have been reported with mild to moderate neurological findings. All patients with types A and B NPD have mutations in the gene encoding ASM (SMPD1), and thus the disease is more accurately referred to as ASM deficiency (ASMD). Herein we will review the clinical, pathological, biochemical, and genetic findings in types A and B NPD, and emphasize the seminal contributions of Dr. Brady to this disease. We will also discuss the current status of therapy for this disorder.

Deep sequencing of SMPD1 gene revealed a heterozygous frameshift mutation (p.Ser192Alafs) in a Palestinian infant with Niemann–Pick disease type A: a case report

“…Niemann–Pick disease (NPD) is an autosomal recessive disease caused by reduced expression of the enzyme acid sphingomyelinase (ASM), encoded by the sphingomyelin phosphodiesterase 1 ( SMPD1 ) gene, resulting in lysosomal accumulation of sphingomyelin in [1, 2] the brain causing irreversible neurological damage. NPD types A and B are estimated to affect 1 in 250,000 individuals.…”

“…NPD types A and B are estimated to affect 1 in 250,000 individuals. Type A is an early-onset neurodegenerative disorder characterized by severe central nervous system deterioration, cherry-red macula, and massive hepatosplenomegaly, leading to death at an early age [3]. Type B is a late-onset non-neuronopathic disease with intermediate clinical presentations that correlate with hepatosplenomegaly and respiratory complications.…”

“…Type B is a late-onset non-neuronopathic disease with intermediate clinical presentations that correlate with hepatosplenomegaly and respiratory complications. Most of these cases survive until adulthood [1, 2]. …”

Liver Transplantation for Lysosomal Storage Disorders: A Novel Option to Pick

“…Elevated serum chitotriosidase, hyperlipidemia (increased low‐density lipoprotein and very low density lipoprotein with low high‐density lipoprotein), infiltrative interstitial pulmonary disease, cardiac and retinal disease (cherry red spot maculae), growth retardation, cytopenia, and skeletal involvement (osteopenia/osteoporosis and joint pain) are the hallmarks of the disease. Although in the liver the condition involves mainly the reticuloendothelial system, foamy inclusions are present also in the hepatocytes and in the bile duct epithelium of these patients …”

“…At present, a phase 2 trial has been started also for pediatric patients (NCT02292654). Even if ERT seems to be effective on visceral symptoms, it is important to evaluate new therapeutic approaches for neurological disease because olipudase alfa does not cross the blood‐brain barrier . Because of the systemic expression of the disease, liver transplantation (LT) has been considered ineffective in NPD type B, with only 2 cases of LT in 2 adults being reported so far …”