Natural history of Niemann-Pick disease type C in a multicentre observational retrospective cohort study

Wraith, J. E.; Guffon, Nathalie; Rohrbach, Marianne; Hwu, Wuh‐Liang; Korenke, Georg Christoph; Bembi, Bruno; Luzy, Cécile; Giorgino, R.; Sedel, Frédéric

doi:10.1016/j.ymgme.2009.06.009

Cited by 94 publications

(96 citation statements)

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“…Niemann-Pick disease type C (NP-C) is a rare inherited disease, caused by mutations in either the NPC1 or the NPC2 gene, which leads to impaired intracellular lipid trafficking and the accumulation of cholesterol and glycosphingolipids in the brain and other tissues [1][2][3][4][5][6] . The clinical signs and symptoms of NP-C can develop at any age, and significant phenotypic heterogeneity is frequently observed in NP-C 1,2,4-7 .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Conclusão: Embora coloração de filipina seja utilizada para confirmar o diagnóstico, o histiócito azul-marinho no aspirado de medula óssea frequentemente auxilia a confirmar o diagnóstico de NP-C. A mutação p.P1007A está correlacionada com o padrão " variante" na coloração de filipina. A resposta ao tratamento com miglustate parece estar correlacionada com a idade e escore de desabilidade no momento do diagnóstico.Palavras-chave: doença de Niemann-Pick tipo C, medula óssea, coloração de filipina, gene NPC1, miglustate.Niemann-Pick disease type C (NP-C) is a rare inherited disease, caused by mutations in either the NPC1 or the NPC2 gene, which leads to impaired intracellular lipid trafficking and the accumulation of cholesterol and glycosphingolipids in the brain and other tissues [1][2][3][4][5][6] . The clinical signs and symptoms of NP-C can develop at any age, and significant phenotypic heterogeneity is frequently observed in NP-C 1,2,4-7 .…”

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“…NP-C patients often show sea-blue histiocytes or foamy cells in bone marrow analyses and intracellular lipid accumulation with filipin staining 1,3,4,6,7 . Molecular analyses typically show NPC1 (in 95% of cases) or NPC2 (in around 4% of cases) gene mutations [1][2][3][4]6,7 .…”

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confidence: 99%

“…Molecular analyses typically show NPC1 (in 95% of cases) or NPC2 (in around 4% of cases) gene mutations [1][2][3][4]6,7 . Nevertheless, vertical supranuclear gaze palsy, cataplexia, high chitotriosidase serum level and relatives with similar symptoms are also considered to be clinical clues pointing to the diagnosis [4][5][6][7] .…”

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Niemann-Pick disease type C: a case series of Brazilian patients

Lorenzoni

Cardoso

Crippa

et al. 2014

Arq. Neuro-Psiquiatr.

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The aim of the study was to analyze a series of Brazilian patients with Niemann-Pick disease type C (NP-C). Method: Correlations between clinical findings, laboratory data, molecular findings and treatment response are presented. Result: The sample consisted of 5 patients aged 8 to 26 years. Vertical supranuclear gaze palsy, cerebellar ataxia, dementia, dystonia and dysarthria were present in all cases. Filipin staining showed the "classical" pattern in two patients and a "variant" pattern in three patients. Molecular analysis found mutations in the NPC1 gene in all alleles. Miglustat treatment was administered to 4 patients. Conclusion: Although filipin staining should be used to confirm the diagnosis, bone marrow sea-blue histiocytes often help to diagnosis of NP-C. The p.P1007A mutation seems to be correlated with the "variant" pattern in filipin staining. Miglustat treatment response seems to be correlated with the age at disease onset and disability scale score at diagnosis.Keywords: Niemann-Pick disease type C, bone marrow, filipin stain, NPC1gene, miglustat.RESUMO O objetivo desse estudo foi analisar uma série de casos de pacientes brasileiros com doença de Niemann-Pick tipo C (NP-C). Método: Correlação entre manifestações clínicas, alterações laboratoriais, estudo molecular e resposta ao tratamento foram realizadas. Resultado: A amostra consiste de 5 pacientes com idade entre 8 e 26 anos. Paralisia do olhar vertical supranuclear, ataxia cerebelar, demência, distonia e disartria estavam presentes em todos os casos. Coloração de filipina na cultura de fibroblastos mostrou padrão "clássico" em dois pacientes e padrão "variante" em três casos. O estudo molecular encontrou mutações no gene NPC1 em todos os alelos. O tratamento com miglustate foi realizado em 4 pacientes. Conclusão: Embora coloração de filipina seja utilizada para confirmar o diagnóstico, o histiócito azul-marinho no aspirado de medula óssea frequentemente auxilia a confirmar o diagnóstico de NP-C. A mutação p.P1007A está correlacionada com o padrão " variante" na coloração de filipina. A resposta ao tratamento com miglustate parece estar correlacionada com a idade e escore de desabilidade no momento do diagnóstico.Palavras-chave: doença de Niemann-Pick tipo C, medula óssea, coloração de filipina, gene NPC1, miglustate.Niemann-Pick disease type C (NP-C) is a rare inherited disease, caused by mutations in either the NPC1 or the NPC2 gene, which leads to impaired intracellular lipid trafficking and the accumulation of cholesterol and glycosphingolipids in the brain and other tissues [1][2][3][4][5][6] . The clinical signs and symptoms of NP-C can develop at any age, and significant phenotypic heterogeneity is frequently observed in NP-C 1,2,4-7 . Vertical supranuclear gaze palsy, cerebellar ataxia, dystonia, dementia, epilepsy and visceral manifestations are the most common symptoms of NP-C 1,2,4-7 .NP-C patients often show sea-blue histiocytes or foamy cells in bone marrow analyses and intracellular lipid accumulation with filipin stain...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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mentioning

confidence: 99%

mentioning

confidence: 99%

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Niemann-Pick disease type C: a case series of Brazilian patients

Lorenzoni

Cardoso

Crippa

et al. 2014

Arq. Neuro-Psiquiatr.

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Niemann–Pick Disease

Patterson

2017

Neurodegeneration

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The videofluoroscopic swallowing study shows a sustained improvement of dysphagia in children with Niemann–Pick disease type C after therapy with miglustat

Fecarotta

Amitrano

Romano

et al. 2011

American J of Med Genetics Pt A

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Niemann-Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder characterized by defective intracellular lipid trafficking, with secondary accumulation of free cholesterol, sphingosine, and glycosphingolipids. NPC is clinically characterized by a wide spectrum of manifestations with progressive visceral and neurological involvement, including dysphagia. Neurological manifestations represent the most debilitating findings. Swallowing impairment is a frequent cause of morbidity and disability in NPC patients and progressive dysphagia may be considered a marker of neurological progression. Recently substrate reduction therapy with miglustat has been proposed for the treatment of neurological manifestations in NPC patients. This observational study reports on the long-term use of miglustat in four pediatric patients with NPC and shows the efficacy of the treatment to improve or prevent dysphagia, and persistence after 3 years of treatment or more. We used a videofluoroscopic analysis of liquid barium swallowing to provide additional information on patterns of impairment of the swallowing mechanism and to detect aspiration. In three patients showing dysphagia and aspiration we observed the improvement of the swallowing function and the sustained absence of barium aspiration in the airways after miglustat treatment, while the patient with normal swallowing function at baseline did not show any deterioration. We suggest that the videofluoroscopic study of swallowing should be routinely used to monitor the effects of treatment on swallowing ability in NPC patients.

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Natural history of Niemann-Pick disease type C in a multicentre observational retrospective cohort study

Cited by 94 publications

References 23 publications

Niemann-Pick disease type C: a case series of Brazilian patients

Niemann-Pick disease type C: a case series of Brazilian patients

Niemann–Pick Disease

The videofluoroscopic swallowing study shows a sustained improvement of dysphagia in children with Niemann–Pick disease type C after therapy with miglustat

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