A quantitative assessment of the evolution of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-C
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RESEARCH
Open Access
A quantitative assessment of the evolution of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2CDG) Natalia Lourdes Serrano1,2,3, Victor De Diego1,2, Daniel Cuadras4, Antonio F. Martinez Monseny5, Ramón Velázquez-Fragua6, Laura López7, Ana Felipe8, Luis G. Gutiérrez-Solana7, Alfons Macaya8, Belén Pérez-Dueñas1,2, Mercedes Serrano1,2,5,9* and CDG Spanish-Consortium
Abstract Background: We aim to delineate the progression of cerebellar syndrome in children with phosphomannomutasedeficiency (PMM2-CDG) using the International Cooperative Ataxia Rating Scale (ICARS). We sought correlation between cerebellar volumetry and clinical situation. We prospectively evaluated PMM2-CDG patients aged from 5 to 18 years through ICARS at two different time points set apart by at least 20 months. We reviewed available MRIs and performed volumetric analysis when it was possible. Results: From the eligible 24, four patients were excluded due to severe mental disability (n = 2) and supratentorial lesions (n = 2). Two different ICARS evaluations separated by more than 20 months were available for 14 patients showing an improvement in the cerebellar syndrome: ICARS1: 35.71 versus ICARS2: 30.07 (p < 0.001). When we considered time, we saw an improvement of 2.64 points in the ICARS per year with an SD of 1.97 points (p < 0.001). The ICARS subscales results improved with time, reaching statistical significance in “Posture and gait” (p < 0.001), “Kinetic functions” (p = 0.04) and “Speech abnormalities” (p = 0.045). We found a negative correlation between the ICARS results and total cerebellar volume (r = −0.9, p = 0.037) in a group of five patients with available volumetric study, meaning that the higher the ICARS score, the more severe was the cerebellar atrophy. Conclusions: Our study shows a stabilization or mild improvement in the cerebellar functions of paediatric PMM2-CDG patients despite cerebellar volume loss. ICARS is a valid scale to quantify the evolution of cerebellar syndrome in PMM2CDG patients. The availability of ICARS and other reliable and sensitive follow-up tools may prove essential for the evaluation of potential therapies. Keywords: Cerebellum, Congenital disorders of glycosylation, Developmental disorders, Gait disorders/ataxia, ICARS, MRI
Background Phosphomannomutase deficiency (PMM2-CDG), is caused by mutations in PMM2 (MIM *#601,785), and is the most frequent congenital disorder of N-linked glycosylation [1]. Patients with PMM2-CDG develop a cerebellar syndrome with axial and peripheral ataxia, * Correspondence: [email protected] 1 Neuropediatric, Radiology and Clinical Biochemistry Departments, Hospital Sant Joan de Déu, Barcelona, Spain 2 U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Barcelona, Spain Full list of author information is available at the end of the article
abnormal eye movements, dysarthria, and cognitive deficits which cause long-term disability [2]. Brain MRIs and neuropathological studies show a
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