Search results for "Niemann-Pick Disease"
showing 10 items of 17 documents
Consensus recommendation for a diagnostic guideline for acid sphingomyelinase deficiency
2017
Disclaimer: This diagnostic guideline is intended as an educational resource and represents the opinions of the authors, and is not representative of recommendations or policy of the American College of Medical Genetics and Genomics (ACMG). The information should be considered a consensus based on expert opinion, as more comprehensive levels of evidence were not available in the literature in all cases. Background: Acid sphingomyelinase deficiency (ASMD) is a rare, progressive, and often fatal lysosomal storage disease. The underlying metabolic defect is deficiency of the enzyme acid sphingomyelinase that results in progressive accumulation of sphingomyelin in target tissues. ASMD manifests…
Lysosomal acid lipase deficiency: Expanding differential diagnosis.
2016
The differential diagnoses for metabolic liver diseases may be challenging in clinical settings, which represents a critical issue for disorders such as lysosomal acid lipase deficiency (LAL-D). LAL-D is caused by deficient activity of the LAL enzyme, resulting in the accumulation of cholesteryl esters and triglycerides throughout the body, predominately in the liver, spleen, gastrointestinal tract, and blood vessel walls. LAL-D is a progressive, multi-organ disease with early mortality and significant morbidity characterized by a combination of hepatic dysfunction and dyslipidemia. Evidence suggests LAL-D may be substantially underdiagnosed or misdiagnosed, which is critical given that dis…
Recommendations for clinical monitoring of patients with acid sphingomyelinase deficiency (ASMD)
2018
Abstract Background Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, results from mutations in SMPD1, the gene encoding acid sphingomyelinase (ASM). As a result, sphingomyelin accumulates in multiple organs including spleen, liver, lung, bone marrow, lymph nodes, and in the most severe form, in the CNS and peripheral nerves. Clinical manifestations range from rapidly progressive and fatal infantile neurovisceral disease, to less rapidly progressing chronic neurovisceral and visceral forms that are associated with significant morbidity and shorter life span due to respiratory or liver disease. Objectives To provide a contemporary guide of clinical assessments for di…
Isocortical Pathology in Type C Niemann-Pick Disease
1983
A case of Niemann-Pick disease was examined with Golgi preparations and a transparent Golgi impregnation counterstained for intraneuronal pigment deposits. There was a specific type of storage of unmetabolized substrate restricted to certain nerve cell types. The most conspicuous changes in the isocortex were: 1) dilated axonal segments in layer IIIab pyramidal cells filled with storage material; the volume of these axonal expansions often exceeded that of the soma; 2) distension of layer IIIc, layer V, and layer VIa pyramidal cell perikarya with storage material; 3) new formation, elongation, and vertical orientation of basal dendrites in layer V pyramidal cells; 4) well-preserved pyramida…
AISF update on the diagnosis and management of adult-onset lysosomal storage diseases with hepatic involvement.
2020
Lysosomal storage diseases (LSDs) are a heterogeneous group of inherited disorders caused by loss-of-function mutations in genes encoding for lysosomal enzymes/proteins. The consequence is a progressive accumulation of substrates in these intracellular organelles, resulting in cellular and tissue damage. The overall incidence is about 1/8000 live births, but is likely underestimated. LSDs are chronic progressive multi-systemic disorders, generally presenting with visceromegaly, and involvement of the central nervous system, eyes, the skeleton, and the respiratory and cardiovascular systems. The age at onset and phenotypic expression are highly variable, according to the specific enzymatic d…
Type B Niemann-Pick Disease: Findings at Chest Radiography, Thin-Section CT, and Pulmonary Function Testing
2005
To evaluate findings at radiography, computed tomography (CT), and pulmonary function testing in patients with type B Niemann-Pick disease.The study was approved by the institutional review board or ethics committee at each study site and was compliant with HIPAA at the U.S. site. Written informed consent was obtained from each patient or guardian and minor assent was obtained from all children before any study-related procedures. Pulmonary involvement in 53 patients (27 male and 26 female patients; age range, 7-65 years; mean age, 23.3 years) with type B Niemann-Pick disease was evaluated with imaging and pulmonary function tests. All patients underwent chest radiography and thin-section C…
Psychiatric and neurological symptoms in patients with Niemann-Pick disease type C (NP-C): Findings from the International NPC Registry
2017
Objectives: Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease that should be recognised by psychiatrists as a possible underlying cause of psychiatric abnormalities. This...
Acetyl-dl-leucine in Niemann-Pick type C
2015
Objective: To assess the effects of the modified amino acid acetyl-dl-leucine (AL) on cerebellar ataxia, eye movements, and quality of life of patients with Niemann-Pick type C (NP-C) disease. Methods: Twelve patients with NP-C disease were treated with AL 3 g/d for 1 week and then with 5 g/d for 3 weeks with a subsequent washout period of 1 month. The Scale for the Assessment and Rating of Ataxia (SARA), the Spinocerebellar Ataxia Functional Index (SCAFI), the modified Disability Rating Scale (mDRS), EuroQol 5Q-5D-5L, and the visual analog scale (VAS) were administered. Measurements took place at baseline, after 1 month of therapy, and after 1 month of washout. Results: The SARA score chan…
Recommendations on the diagnosis and management of Niemann-Pick disease type C
2009
Niemann-Pick disease type C (NP-C) is a lysosomal storage disease in which impaired intracellular lipid trafficking leads to excess storage of cholesterol and glycosphingolipids in the brain and other tissues. it is characterized clinically by a variety of progressive, disabling neurological symptoms including clumsiness, limb and gait ataxia, dysarthria, dysphagia and cognitive deterioration (dementia). Until recently, there has been no disease-modifying therapy available for NP-C, with treatment limited to supportive measures. In most countries, NP-C is managed through specialist centers, with non-specialist support provided locally. However, effective patient Support is hampered by the a…
Reduced VLDL clearance in ApoeNpc1 mice is associated with increased Pcsk9 and Idol expression and decreased hepatic LDL-receptor levels
2010
Niemann-Pick type C1 (NPC1) promotes the transport of LDL receptor (LDL-R)-derived cholesterol from late endosomes/lysosomes to other cellular compartments. NPC1-deficient cells showed impaired regulation of liver_X receptor (LXR) and sterol regulatory element-binding protein (SREBP) target genes. We observed that Apoe(-/-)Npc1(-/-) mice displayed a marked increase in total plasma cholesterol mainly due to increased VLDL, reflecting decreased clearance. Although nuclear SREBP-2 and Ldlr mRNA levels were increased in Apoe(-/-)Npc1(-/-) liver, LDL-R protein levels were decreased in association with marked induction of proprotein convertase subtilisin/kexin type 9 (Pcsk9) and inducible degrade…