The natural history of Niemann–Pick disease type C in the UK

Abstract

Niemann-Pick disease type C (NPC) is an autosomal recessive, neurovisceral lipid storage disorder. Mutations in two genes (NPC1 and NPC2) produce indistinguishable clinical phenotypes by biochemical mechanisms that have not yet been entirely clarified. The wide spectrum of clinical presentations of NPC includes hepatic and pulmonary disease as well as a range of neuropsychiatric disorders. Late-onset disease has been increasingly recognized as the biochemical diagnosis of NPC has been more widely applied in adult neurology clinics. The clinical presentation and follow-up of 94 patients with NPC is described, 58 of whom were still alive at the time this report was prepared. The age at diagnosis ranged from the prenatal period (with hydrops fetalis) up to 51 years. This review of NPC patients in the UK confirms the phenotypic variability of this inherited lipid storage disorder reported elsewhere. Although a non-neuronopathic variant has been described, most patients in this series who survived childhood inevitably suffered neurological and in some cases neuropsychiatric deterioration. While symptomatic treatment, such as anticholinergic and antiepileptic drugs, can alleviate some aspects of the disease, there is a clear need to develop a specific treatment for this progressively debilitating neurodegenerative disorder.

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

“…However, Paciorkowski and colleagues recently reported the case of a 3-yearold child who did not benefit from 12 months of miglustat treatment (Paciorkowski et al 2008). The non-responsiveness to the treatment in Paciorkowski_s patient could be due to the fact that patients with neonatal-onset NPC have a more severe clinical course than patients with later-onset forms (Imrie et al 2007). Since the initial manifestations of NPC disease vary, with systemic (hepatic, splenic and pulmonary) and neurological symptoms taking independent courses (Sevin et al 2007), it may be reasonable in the neonatal-onset severe type to start treatment with medications that lower somatic cholesterol, add to miglustat subsequently or concomitantly.…”

Special considerations in children

“…In the first months of life it is part of the neonatal cholestasis syndrome, being the second most common genetic cause behind A1AT deficiency, explaining 8% of cases of "neonatal cholestasis," and 25% of "neonatal hepatitis-like syndrome" [68,69]. Affected infants can exhibit signs of severe liver impairment like ascites, jaundice, and hepatomegaly.…”

Morbus Niemann-Pick Typ C

“…Er manifestiert sich primär mit viszeralen Befunden. Der fortschreitende neurodegenerative Verlauf beginnt häufig Jahre, mitunter Jahrzehnte später und korreliert nicht direkt mit der viszeralen Ausprägung [6,7,12,23].…”