Web of Science: 42 cites, Scopus: 47 cites, Google Scholar: cites,
Phosphomannomutase deficiency (PMM2-CDG) : ataxia and cerebellar assessment
Serrano, Mercedes (Centro de Investigación Biomédica en Red de Enfermedades Raras)
De Diego, Victor (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Muchart, Jordi (Institut de Recerca Sant Joan de Déu)
Cuadras, Daniel (Statistics Department, Fundació Sant Joan de Déu)
Felipe-Rucián, Ana (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Macaya Ruiz, Alfons (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Velázquez-Fragua, Ramón (Hospital Universitario La Paz (Madrid))
Poo, M. Pilar (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Fons, Carmen (Centro de Investigación Biomédica en Red de Enfermedades Raras)
O'Callaghan, Maria del Mar (Centro de Investigación Biomédica en Red de Enfermedades Raras)
García-Cazorla, Angels (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Boix, Cristina (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Robles, Bernabé (Hospital Sant Joan de Déu (Manresa))
Carratalá, Francisco (Neurology Department, Hospital Sant Joan d'Alacant)
Girós, Marisa (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Briones, Paz (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Gort, Laura (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Artuch, R. (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Pérez-Cerdá, Celia (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Jaeken, Jaak (Center for Metabolic Disease, KULeuven)
Pérez, Belén (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Pérez-Dueñas, Belén (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Universitat Autònoma de Barcelona
Vall d'Hebron Institut de Recerca (VHIR)

Data: 2015
Resum: Phosphomannomutase deficiency (PMM2-CDG) is the most frequent congenital disorder of glycosylation. The cerebellum is nearly always affected in PMM2-CDG patients, a cerebellar atrophy progression is observed, and cerebellar dysfunction is their main daily functional limitation. Different therapeutic agents are under development, and clinical evaluation of drug candidates will require a standardized score of cerebellar dysfunction. We aim to assess the validity of the International Cooperative Ataxia Rating Scale (ICARS) in children and adolescents with genetically confirmed PMM2-CDG deficiency. We compare ICARS results with the Nijmegen Pediatric CDG Rating Scale (NPCRS), neuroimaging, intelligence quotient (IQ) and molecular data. Our observational study included 13 PMM2-CDG patients and 21 control subjects. Ethical permissions and informed consents were obtained. Three independent child neurologists rated PMM2-CDG patients and control subjects using the ICARS. A single clinician administered the NPCRS. All patients underwent brain MRI, and the relative diameter of the midsagittal vermis was measured. Psychometric evaluations were available in six patients. The Mann-Whitney U test was used to compare ICARS between patients and controls. To evaluate inter-observer agreement in patients' ICARS ratings, intraclass correlation coefficients (ICC) were calculated. ICARS internal consistency was evaluated using Cronbach's alpha. Spearman's rank correlation coefficient test was used to correlate ICARS with NPCRS, midsagittal vermis relative diameter and IQ. ICARS and ICARS subscores differed between patients and controls (p < 0. 001). Interobserver agreement of ICARS was "almost perfect" (ICC = 0. 99), with a "good" internal reliability (Cronbach's alpha = 0. 72). ICARS was significantly correlated with the total NPCRS score (r 0. 90, p < 0. 001). However, there was no agreement regarding categories of severity. Regarding neuroimaging, inverse correlations between ICARS and midsagittal vermis relative diameter (r −0. 85, p = 0. 003) and IQ (r −0. 94, p = 0. 005) were found. Patients bearing p. E93A, p. C241S or p. R162W mutations presented a milder phenotype. ICARS is a reliable instrument for assessment of PMM2-CDG patients, without significant inter-rater variability. Despite our limited sample size, the results show a good correlation between functional cerebellar assessment, IQ and neuroimagingFor the first a correlation between ICARS, neuroimaging and IQ in PMM2-CDG patients has been demonstrated.
Ajuts: Ministerio de Economía y Competitividad U-746, U-737 and U703
Instituto de Salud Carlos III PI14/00021
Instituto de Salud Carlos III PI11/01096
Instituto de Salud Carlos III PI11/01250
Instituto de Salud Carlos III PI10/00455
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Cerebellum ; Congenital disorders of glycosylation ; Developmental disorders ; Gait disorders/ataxia ; MRI ; Neuropsychological assessment
Publicat a: Orphanet Journal of Rare Diseases, Vol. 10 (october 2015) , ISSN 1750-1172

DOI: 10.1186/s13023-015-0358-y
PMID: 26502900


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