Date: 11 Dec 2006
The natural history of Niemann–Pick disease type C in the UK
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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.
Communicating editor: Michael Gibson
Competing interests: None declared
An erratum to this article is available at http://dx.doi.org/10.1007/s10545-007-9986-2.
Butler JD, Blanchette-Mackie J, Goldin E, etal (1992) Progesterone blocks cholesterol translocation from lysosomes. J Biol Chem 267: 2797–2805.
Grau AJ, Weisbrod M, Niethammer R, etal (1997) Niemann-Pick disease Type C mimicking features of multiple sclerosis. J Neurol/Neurosurg Psych 63: 552.
Kelly DA, Portmann B, Mowat AP, etal (1994) Niemann–Pick disease type C: diagnosis and outcome in children, with particular reference to liver disease. J Pediatr 124: 665–666.
Mieli-Vergani G, Howard ER, Mowat AP (1991) Liver disease in infancy: a 20 year perspective. Gut Suppl S121–128.
Patterson MC, Di Bisceglie AM, Higgins, etal (1993) The effect of cholesterol-lowering agents on hepatic and plasma cholesterol in Niemann–Pick disease type C. Neurology 43: 61–64.PubMed
Patterson MC, Vanier MT, Suzuki K, etal (2001) Niemann–Pick disease type C: a lipid trafficking disorder. In: Scriver CR, Beaudetal Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc, eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 3611–3633.
Patterson M, Vecchio D, Prady H, Ait-Aussa N, Abel L, Wraith E (2005) Oral miglustat in adult and pediatric patients with Niemann–Pick type C (NPC) disease: rationale, methodology and interim analyses of a clinical study. American Society for Human Genetics, Salt Lake City, October 2005 [Poster].
Steinberg SJ, Ward CP, Fensom AH (1994) Complementation studies in Niemann–Pick disease type C indicate the existence of a second group. Med Genet 31: 317–320.CrossRef
Trendleburg G, Vanier MT, Maza S, etal (2006) Niemann–Pick type C disease in a 68-year-old patient. J Neurol Neurosurg Psychiatry 77: 997–998.CrossRef
Vanier MT, Millat G (2004) Structure and function of the NPC2 protein. Biochim Biophys Acta 1685: 14–21.PubMed
Vanier MT, Rodriguez-Lafrasse C, Rousson R, etal (1991) Type C Niemann–Pick disease: spectrum of phenotypic variation in disruption of intracellular LDL-derived cholesterol processing. Biochim Biophys Acta 1096: 1328.
- The natural history of Niemann–Pick disease type C in the UK
Journal of Inherited Metabolic Disease
Volume 30, Issue 1 , pp 51-59
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- 1. Willink Biochemical Genetics Unit, Royal Manchester Children’s Hospital, Manchester, UK
- 2. Inserm U189, Faculté de Médecine Lyon-Sud, Oullins Cedex
- 3. Laboratoire Fondation Gillet-Mérieux, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
- 4. Genetics Centre, Guys Hospital, St Thomas St, London, UK