Differences in Niemann-Pick disease type C symptomatology observed in patients of different ages

dc.contributor.authorMengel, Eugen
dc.contributor.authorPineda, Mercedes
dc.contributor.authorHendriksz, Christian J.
dc.contributor.authorWalterfang, Mark
dc.contributor.authorTorres, Juan V.
dc.contributor.authorKolb, Stefan A.
dc.date.accessioned2017-03-27T08:28:15Z
dc.date.available2017-03-27T08:28:15Z
dc.date.issued2017-03
dc.description.abstractBACKGROUND : Niemann-Pick disease Type C (NP-C) is a genetic lipid storage disorder characterised by progressive neurovisceral symptomatology. Typically, disease progression ismore pronounced in patientswith early onset of neurological symptoms. Heterogeneous clinical presentation may hinder disease recognition and lead to delays in diagnosis. Here we describe the prevalence of signs and symptoms observed in patientswith NP-C and analyse the relationship between these symptoms in different age groups. METHODS : The combined patient cohort used in the analyses comprised NP-C cases (n=164) and controls (n= 135) aged 0 to 60 years from two previously published cohorts; a cohort of all ages fromwhich patients ≤4 years of agewere excluded and a cohortwith early-onset NP-C and age-matched controls. The analysis of relationships between different signs and symptoms was performed for both NP-C cases and controls in two sub-groups, ≤4 and N4 years of age, using cluster analyses. The threshold of 4 years of age was selected to reflect the minimum age cut-off for satisfactory discriminatory power of the original NP-C SI. To assess the prevalence of individual signs and symptoms at age of diagnosis, patientswere categorised by age into 5-year sub-groups, and prevalence values estimated for each sign and symptom of NP-C. RESULTS : Twomain clusters of symptomswere clearly defined for NP-C cases in each age sub-group,whereas clusters were not as clearly defined for controls. For NP-C cases ≤4 years of age, one cluster comprised exclusively visceral symptoms; the second cluster combined all other signs and symptoms in this age group. For NP-C cases N4 years of age, each cluster contained amixture of visceral, neurological and psychiatric items. Prevalence estimations showed that visceral symptoms (e.g. isolated unexplained splenomegaly)were most common inNPC cases ≤4 years of age. Neurological symptoms were generallymore common in NP-C cases N4 years of age than in younger patients, with the exception of hypotonia and delayed developmental milestones. CONCLUSIONS : These analyses provide a comprehensive overviewof symptomatology observed in a large combined cohort of patients with NP-C and controls across a wide range of ages. The results largely reflect observations from clinical practice and support the importance of multi-disciplinary approaches for identification of patients with NP-C, taking into account age-specific manifestations and their possible correlations.en_ZA
dc.description.departmentPaediatrics and Child Healthen_ZA
dc.description.librarianam2017en_ZA
dc.description.sponsorshipManuscript preparation for this publication was supported by Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.en_ZA
dc.description.sponsorshipEM,MP, CJH,MWand JVT have received consulting fees or honoraria from Actelion Pharmaceuticals Ltd.en_ZA
dc.description.urihttp://www.elsevier.com/locate/ymgmeen_ZA
dc.identifier.citationMengel, E, Pineda, M, Hendriksz, CJ, Walterfang, M, Torres, JV & Kolb, SA 2017, 'Differences in Niemann-Pick disease type C symptomatology observed in patients of different ages', Molecular Genetics and Metabolism, vol. 120, no. 3, pp. 180-189.en_ZA
dc.identifier.issn1096-7192 (print)
dc.identifier.issn1096--7206 (online)
dc.identifier.other10.1016/j.ymgme.2016.12.003
dc.identifier.urihttp://hdl.handle.net/2263/59548
dc.language.isoenen_ZA
dc.publisherElsevieren_ZA
dc.rights© 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license.en_ZA
dc.subjectPrevalenceen_ZA
dc.subjectClusteren_ZA
dc.subjectDiagnosisen_ZA
dc.subjectClinical featuresen_ZA
dc.subjectSymptomsen_ZA
dc.subjectNiemann-Pick disease type C (NP-C)en_ZA
dc.titleDifferences in Niemann-Pick disease type C symptomatology observed in patients of different agesen_ZA
dc.typeArticleen_ZA

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