Cause of death in patients with chronic visceral and chronic neurovisceral acid sphingomyelinase deficiency (Niemann-Pick disease type B and B variant): Literature review and report of new cases

Cassiman, David; Packman, Seymour; Bembi, Bruno; Turkia, Hadhami Ben; Al-Sayed, Moeenaldeen; Schiff, Manuel; Imrie, Jackie; Mabe, Paulina; Takahashi, Tsutomu; Mengel, Karl Eugen; Giugliani, Roberto; Cox, Gerald F.

doi:10.1016/j.ymgme.2016.05.001

Cited by 90 publications

(149 citation statements)

References 36 publications

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“…Some patients with type B NPD can develop significant life-threatening complications of their disease, including liver failure, hemorrhage, oxygen dependency, pulmonary infections, and splenic rupture [28,29]. Some develop coronary artery or valvular heart disease.…”

Section: Natural Historymentioning

confidence: 99%

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Types A and B Niemann-Pick disease

Schuchman

Desnick

2017

Molecular Genetics and Metabolism

223

186

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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.

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Section: Natural Historymentioning

confidence: 99%

“…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., 14,16–18,28,29]. …”

Section: Natural Historymentioning

confidence: 99%

Types A and B Niemann-Pick disease

Schuchman

Desnick

2017

Molecular Genetics and Metabolism

223

186

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Section: Natural Historymentioning

confidence: 99%

Types A and B Niemann-Pick disease

Schuchman¹,

Wasserstein²

2015

Best Practice & Research Clinical Endocrinology & Metab

120

136

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“…[5] While most affected NBIA genes result in abnormalities in mitochondrial lipid metabolism, the question of how this biochemical pathway alterations relate to brain iron accumulation is still debated. [4] Here we present a case of NP-B characterized by severe deficiency in the sphingomyelinase enzyme activity, hepatosplenomegaly and pulmonary fibrosis, without clinical signs of neurological impairment, [6] but with marked accumulation of iron in the autopsied brain. The question arose whether this significant cerebral iron deposition was secondary to the lipid dysmetabolism involving sphingomyeline and ceramide in NP-B, or it was rather part of a second rare disease caused by an inherited NBIA gene mutation.…”

Section: Introductionmentioning

confidence: 95%

Niemann-Pick’s disease type B and brain iron accumulation

Garzuly

Szabó

Bencsik

et al. 2017

CRCP

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Background: Niemann-Pick's type B (NP-B) disease is a rare, autosomal recessive visceral storage disorder related to a lysosomal accumulation of sphingomyelin, which is caused by mutations in the sphingomyelinase gene, SMPD1. Case report: We present a boy who had normal early development, but from one year of age, he showed progressive manifestations of hepatosplenomegaly, somatomotor retardation and cardiopulmonary dysfunction. The activity of the sphingomyelinase enzyme was very low in his fibroblasts. He died at 17 years of age from cardio-respiratory insufficiency. Gross pathology and histology of the internal organs were compatible with Niemann-Pick's disease. His brain and spinal cord displayed no signs of storage disease, confirming the subtype of NP-B. Unexpectedly, however, significant accumulation of iron was seen in the substantia nigra, subthalamic nuclei, putamen, globus pallidus and some cortical regions accompanied by axonal spheroids. Brain iron accumulation is the hallmark of a disease group termed neurodegeneration with brain iron accumulation (NBIA). Sequencing of the known NBIA disease genes was unsuccessful in the proband's DNA isolated from formalin-fixed, paraffin-embedded blocks, but both asymptomatic parents were heterozygous carriers of the same c19orf12 deletion. Conclusions: This case initially raised the question as to whether two rare autosomal recessive disorders, NP-B and a subtype of NBIA could have co-occurred in our patient, or the lipid dysmetabolism due to sphingomyelinase deficiency caused secondary brain iron accumulation. Genetic analyses in the parents suggested the former possibility by identifying a c19orf12 gene deletion known to underlie in homozygous state Mitochondrial Membrane Protein Associated Neurodegeneration.

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Cause of death in patients with chronic visceral and chronic neurovisceral acid sphingomyelinase deficiency (Niemann-Pick disease type B and B variant): Literature review and report of new cases

Abstract: The analysis emphasizes that treatment goals for patients with chronic visceral and chronic neurovisceral ASMD should include reducing splenomegaly and improving liver function and respiratory status, with the ultimate goal of decreasing serious morbidity and mortality.

Cited by 90 publications

References 36 publications

Types A and B Niemann-Pick disease

Types A and B Niemann-Pick disease

Types A and B Niemann-Pick disease

Niemann-Pick’s disease type B and brain iron accumulation

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