Cost of illness associated with Niemann-Pick disease type C in the UK

Imrie, Jackie; Galani, Carmen; Gairy, Kerry; Lock, Kevin; Hunsche, Elke

doi:10.3111/13696990903245863

Cited by 19 publications

(14 citation statements)

References 22 publications

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“…Data from the International NP-C disease registry and other large observational cohort studies [5,7,27] indicate that approximately two-thirds of patients with NP-C have infantile or juvenile onset of neurological manifestations, while approximately one-third have this condition during adolescence or adulthood. In the Bulgarian cohort, the proportion of patients with adult onset was roughly equal to that with infantile or childhood onset.…”

Section: Discussionmentioning

confidence: 99%

Clinical Spectrum and Genetic Variability in Bulgarian Patients with Niemann-Pick Disease Type C

Chamova

Kirov²,

Guergueltcheva³

et al. 2016

Eur Neurol

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Background: Niemann-Pick disease type C (NP-C) is a rare autosomal-recessive lysosomal storage disorder caused by mutations in either the NPC1 (in 95% of cases) or the NPC2 gene. Methods: In a prospective, observational cohort study, all Bulgarian patients diagnosed with NP-C to date (since 2010) underwent detailed neurological examination and neuro-ophthalmological, neuropsychological and psychiatric evaluations, as well as brain MRI, abdominal ultrasound and hearing tests. Plasma chitotriosidase was also measured, when possible. Results: The Bulgarian national NP-C cohort comprised 11 patients who were diagnosed based on molecular genetic analysis (n = 9) and/or filipin staining of skin fibroblasts (n = 3). The mean age at onset was 14.4 (SD 8.3). Diagnoses were achieved 1-23 years after initial clinical presentation. All patients who underwent genetic mutation analysis were compound heterozygotes: a total of 12 NPC1 mutations were recorded, 5 of which were novel. Two patients had late-infantile onset, 4 had juvenile onset, and the remaining 5 had the adult-onset form of NP-C. Initial symptoms were neurological in 9 patients, visceral in one, and predominantly psychiatric in another. Vertical gaze palsy was present in all patients. Dysarthria, pyramidal involvement, cognitive impairment, and organomegaly with varied severity were observed in 10 of them. Ataxia was present in 9 and dystonia in 7. Four patients had epileptic seizures, and gelastic cataplexy was reported in 5. Brain MRI revealed hyperintense white matter lesions in 5 patients and cortical and/or cerebellar atrophy in 4. Conclusions: This Bulgarian NP-C cohort showed wide variability in terms of NPC1 mutations and predominant forms of neurological involvement. Diagnosing NP-C is challenging, and it was often delayed in this cohort due to the heterogeneity of patients' clinical signs and symptoms.

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Section: Discussionmentioning

confidence: 99%

Clinical Spectrum and Genetic Variability in Bulgarian Patients with Niemann-Pick Disease Type C

Chamova

Kirov²,

Guergueltcheva³

et al. 2016

Eur Neurol

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“…For detailed guidelines on current management of patients, the reader is referred to a recent publication compiled by an international working group [27]. A study on the cost of illness associated with NP-C in the UK has recently been published [109]. …”

Section: Management Including Treatmentmentioning

confidence: 99%

Niemann-Pick disease type C

Vanier

2010

Orphanet J Rare Dis

1,001

1,069

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Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120 000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in infancy or childhood). The first neurological symptoms vary with age of onset: delay in developmental motor milestones (early infantile period), gait problems, falls, clumsiness, cataplexy, school problems (late infantile and juvenile period), and ataxia not unfrequently following initial psychiatric disturbances (adult form). The most characteristic sign is vertical supranuclear gaze palsy. The neurological disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures and dystonia are other common features. NP-C is transmitted in an autosomal recessive manner and is caused by mutations of either the NPC1 (95% of families) or the NPC2 genes. The exact functions of the NPC1 and NPC2 proteins are still unclear. NP-C is currently described as a cellular cholesterol trafficking defect but in the brain, the prominently stored lipids are gangliosides. Clinical examination should include comprehensive neurological and ophthalmological evaluations. The primary laboratory diagnosis requires living skin fibroblasts to demonstrate accumulation of unesterified cholesterol in perinuclear vesicles (lysosomes) after staining with filipin. Pronounced abnormalities are observed in about 80% of the cases, mild to moderate alterations in the remainder ("variant" biochemical phenotype). Genotyping of patients is useful to confirm the diagnosis in the latter patients and essential for future prenatal diagnosis. The differential diagnosis may include other lipidoses; idiopathic neonatal hepatitis and other causes of cholestatic icterus should be considered in neonates, and conditions with cerebellar ataxia, dystonia, cataplexy and supranuclear gaze palsy in older children and adults. Symptomatic management of patients is crucial. A first product, miglustat, has been granted marketing authorization in Europe and several other countries for specific treatment of the neurological manifestations. The prognosis largely correlates with the age at onset of the neurological manifestations.

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“…Only one study was identified explicitly quantifying costs of any of the histiocytosis syndromes, focusing on Niemann-Pick disease (NPD) with a comprehensive breakdown of direct (medical and non-medical) and indirect costs (34). …”

Section: Histiocytosismentioning

confidence: 99%

Socio-economic burden of rare diseases: A systematic review of cost of illness evidence

2015

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A c c e p t e d M a n u s c r i p t 2 Highlights  We systematically reviewed the socioeconomic cost literature for 10 rare diseases. Direct and indirect costs incurred by patients, carers and society were searched. 77 studies were included with an unequal distribution of studies over disease types. Level of existing evidence is highest for diseases with available drug treatments. Indirect costs are in most cases of similar or higher magnitude than direct costs. found to range between 1-2 per 100,000 population (PWS, a sub-type of Histiocytosis, and EB) up to 42 per 100,000 population (Scleroderma). Overall, cost evidence on rare diseases appears to be very scarce (a total of 77 studies were identified across all diseases), with CF (n=29) and Haemophilia (n=22) being relatively well studied, compared to the other conditions, where very limited cost of illness information was available. In terms of data availability, total lifetime cost figures were found only across four diseases, and total annual costs (including indirect costs) across five diseases.Overall, data availability was found to correlate with the existence of a pharmaceutical treatment and indirect costs tended to account for a significant proportion of total costs.Although methodological variations prevent any detailed comparison between conditions, most of the rare diseases examined are associated with significant economic burden, both direct and indirect.

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Cost of illness associated with Niemann-Pick disease type C in the UK

Cited by 19 publications

References 22 publications

Clinical Spectrum and Genetic Variability in Bulgarian Patients with Niemann-Pick Disease Type C

Clinical Spectrum and Genetic Variability in Bulgarian Patients with Niemann-Pick Disease Type C

Niemann-Pick disease type C

Socio-economic burden of rare diseases: A systematic review of cost of illness evidence

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