Treatment of a child diagnosed with Niemann–Pick disease type C with miglustat: A case report in Brazil

Santos, Mateus Augusto Silva; Raskin, Salmo; Telles, D. S.; Löhr, Alfredo; Liberalesso, Paulo Breno Noronha; Vieira, Sabas Carlos; Cordeiro, Mara L.

doi:10.1007/s10545-008-0923-9

Cited by 34 publications

(26 citation statements)

References 16 publications

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“…In general, our findings appear in line with those from previous clinical trial data [4,18,19] and case reports [23,25,27] on the effects of miglustat on neurological disease manifestations in paediatric NP-C patients. Based on clinical assessments in a 24-month study of miglustat in children aged 4–12 years, Patterson et al reported stabilization of SEM, an accepted marker of early neurological deterioration in NP-C, in 67% of patients throughout therapy [18].…”

Section: Discussionsupporting

confidence: 92%

“…loperamide). In particular, dietary modifications such as reduced consumption of dietary sucrose, maltose and lactose have been shown to improve the gastrointestinal tolerability of miglustat, and to reduce the magnitude of any changes in body weight, particularly if initiated at or before the start of therapy [33,34]. Finally, observed factors that appear to contribute to reduced treatment compliance among the youngest patients include the bitter taste of oral miglustat therapy, and the lack of a paediatric galenic form.…”

Section: Discussionmentioning

confidence: 99%

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Miglustat therapy in the French cohort of paediatric patients with Niemann-Pick disease type C

Héron¹,

Valayannopoulos²,

Baruteau

et al. 2012

Orphanet Journal of Rare Diseases

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BackgroundNiemann-Pick disease type C (NP-C) is a rare neurovisceral lysosomal lipid storage disease characterized by progressive neurological deterioration. Published data on the use of miglustat in paediatric patients in clinical practice settings are limited. We report findings from a prospective open-label study in the French paediatric NP-C cohort.MethodsData on all paediatric NP-C patients treated with miglustat in France between October 2006 and December 2010 were compiled. All patients had a confirmed diagnosis of NP-C, and received miglustat therapy according to manufacturer’s recommendations. Pre-treatment and follow-up assessments were conducted according to a standardized protocol.ResultsTwenty children were enrolled; 19 had NPC1 gene mutations and 1 had NPC2 gene mutations. The median age at diagnosis was 1.5 years, and the median age at miglustat initiation was 6.0 years. Eight NPC1 patients had the early-infantile, eight had the late-infantile, and three had the juvenile-onset forms of NP-C. A history of hepatosplenomegaly and/or other cholestatic symptoms was recorded in all 8 early-infantile onset patients, 3/8 late-infantile patients, and 1/3 juvenile onset patients. Brain imaging indicated white matter abnormalities in most patients. The median (range) duration of miglustat therapy was 1.3 (0.6–2.3) years in early-infantile, 1.0 (0.8–5.0) year in late-infantile, and 1.0 (0.6–2.5) year in juvenile onset patients. NP-C disability scale scores indicated either stabilization or improvement of neurological manifestations in 1/8, 6/8, and 1/3 NPC1 patients in these subgroups, respectively. There were no correlations between brain imaging findings and disease course. Mild-to-moderate gastrointestinal disturbances were frequent during the first 3 months of miglustat therapy, but were easily managed with dietary modifications and/or anti-propulsive medication.ConclusionsMiglustat can improve or stabilize neurological manifestations in paediatric patients with the late-infantile and juvenile-onset forms of NP-C. Among early-infantile onset patients, a shorter delay between neurological disease onset and miglustat initiation was associated with an initial better therapeutic outcome in one patient, but miglustat did not seem to modify overall disease course in this subgroup. More experience is required with long-term miglustat therapy in early-infantile onset patients treated from the very beginning of neurological manifestations.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Miglustat therapy in the French cohort of paediatric patients with Niemann-Pick disease type C

Héron¹,

Valayannopoulos²,

Baruteau

et al. 2012

Orphanet Journal of Rare Diseases

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“…Previous results from a controlled clinical trial in adult and juvenile patients with NPC [Patterson et al, 2007] and the pediatric subgroup [Patterson et al, 2010], data from a retrospective clinical study [Pineda et al, 2009] and also from single additional patients on miglustat treatment [Chien et al, 2007;Paciorkowski et al, 2008;Santos et al, 2008;Galanaud et al, 2009] indicated the beneficial effect of miglustat on the progression of neurological manifestations, including dysphagia, although data on improvement of swallowing impairment were limited.…”

Section: Discussionmentioning

confidence: 99%

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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“…The efficacy of miglustat in patients with NP-C has also been demonstrated in a number of case series 41,55,56. In two Taiwanese patients treated with miglustat for one year, cognitive improvement was observed in one patient and liver and spleen volumes and chitotriosidase levels were stabilized in both patients 55.…”

Section: Efficacymentioning

confidence: 76%

New therapies in the management of Niemann-Pick type C disease: clinical utility of miglustat

Wraith

Imrie²

2009

TCRM

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Niemann-Pick disease type C (NP-C) is an autosomal recessive disorder characterized by progressive neurological deterioration leading to premature death. The disease is caused by mutations in one of two genes, NPC1 or NPC2, leading to impaired intracellular lipid transport and build-up of lipids in various tissues, particularly the brain. Miglustat (Zavesca®), a reversible inhibitor of glycosphingolipid synthesis, has recently been authorized in the European Union, Brazil and South Korea for the treatment of progressive neurological symptoms in adult and pediatric patients, and represents the first specific treatment for NP-C. Here we review current data on the pharmacology, efficacy, safety and tolerability of miglustat in patients with NP-C, based on findings from a prospective clinical trial, preclinical and retrospective studies, and case reports. Findings demonstrated clinically relevant beneficial effects of miglustat on neurological disease progression in adult, juvenile and pediatric patients with NP-C, particularly those diagnosed in late childhood (6–11 years) and in juveniles and adults (12 years and older), compared with those diagnosed in early childhood (younger than 6 years). Miglustat therapy was well-tolerated in all age groups. With the approval of miglustat, treatment of patients with NP-C can now be aimed toward stabilizing neurological disease, which is likely the best attainable therapeutic goal for this disorder.

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Treatment of a child diagnosed with Niemann–Pick disease type C with miglustat: A case report in Brazil

Cited by 34 publications

References 16 publications

Miglustat therapy in the French cohort of paediatric patients with Niemann-Pick disease type C

Miglustat therapy in the French cohort of paediatric patients with Niemann-Pick disease type C

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

New therapies in the management of Niemann-Pick type C disease: clinical utility of miglustat

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