TY - JOUR
T1 - Longitudinal volumetric and 2D assessment of cerebellar atrophy in a large cohort of children with phosphomannomutase deficiency (PMM2-CDG)
AU - Collaborators Of The Cdg Spanish-Consortium
AU - de Diego, Víctor
AU - Martínez-Monseny, Antonio F.
AU - Muchart, Jordi
AU - Cuadras, Daniel
AU - Montero, Raquel
AU - Artuch, Rafael
AU - Pérez-Cerdá, Celia
AU - Pérez, Belén
AU - Pérez-Dueñas, Belén
AU - Poretti, Andrea
AU - Serrano, Mercedes
AU - Aguilera-Albesa, Sergio
AU - Candela, Ramón Cancho
AU - Marina, Ma Llanos Carrasco
AU - Carratalá, Francisco
AU - Couce, Ma Luz
AU - Felipe, Ana
AU - García, Óscar
AU - García-Silva, Ma Teresa
AU - Gutiérrez-Solana, Luis G.
AU - Macaya, Alfons
AU - Miranda, Ma Concepción
AU - López, Laura
AU - López-Laso, Eduardo
AU - Póo, M. Pilar
AU - Quijada-Fraile, Pilar
AU - Robles, Bernabé
AU - Sierra-Córcoles, Concepción
AU - Velázquez-Fragua, Ramón
N1 - Funding Information:
We are grateful to the doctors and institutions from the Spanish national network for the study of glycosylation disorders for their collaboration. This work was supported by national grant PI14/00021 from the National Plan on I+D+I, cofinanced by ISC-III (Subdirección General de Evaluación y Fomento de la Investigación Sanitaria) and FEDER (Fondo Europeo de Desarrollo Regional) and IPT-2012-0561-010000 from MINECO.
Funding Information:
We thank the patients and their families for their kind collaboration in all our projects, and particularly in this study. We are grateful to the doctors and institutions from the Spanish national network for the study of glycosylation disorders for their collaboration. This work was supported by national grant PI14/00021 from the National Plan on I+D+I, cofinanced by ISC-III (Subdirecci?n General de Evaluaci?n y Fomento de la Investigaci?n Sanitaria) and FEDER (Fondo Europeo de Desarrollo Regional) and IPT-2012- 0561-010000 from MINECO.
Publisher Copyright:
© 2017, SSIEM.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Objective: We aim to delineate the progression of cerebellar atrophy (the primary neuroimaging finding) in children with phosphomannomutase-deficiency (PMM2-CDG) by analyzing longitudinal MRI studies and performing cerebellar volumetric analysis and a 2D cerebellar measurement. Methods: Statistical analysis was used to compare MRI measurements [midsagittal vermis relative diameter (MVRD) and volume] of children with PMM2-CDG and sex- and age-matched controls, and to determine the rate of progression of cerebellar atrophy at different ages. Results: Fifty MRI studies of 33 PMM2-CDG patients were used for 2D evaluation, and 19 MRI studies were available for volumetric analysis. Results from a linear regression model showed that patients have a significantly lower MVRD and cerebellar volume compared to controls (p < 0.001 and p < 0.001 respectively). There was a significant negative correlation between age and MVRD for patients (p = 0.014). The rate of cerebellar atrophy measured by the loss of MVRD and cerebellar volume per year was higher at early ages (r = −0.578, p = 0.012 and r = −0.323, p = 0.48 respectively), particularly in patients under 11 years (p = 0.004). There was a significant positive correlation between MVRD and cerebellar volume in PMM2-CDG patients (r = 0.669, p = 0.001). Conclusions: Our study quantifies a progression of cerebellar atrophy in PMM2-CDG patients, particularly during the first decade of life, and suggests a simple and reliable measure, the MVRD, to monitor cerebellar atrophy. Quantitative measurement of MVRD and cerebellar volume are essential for correlation with phenotype and outcome, natural follow-up, and monitoring in view of potential therapies in children with PMM2-CDG.
AB - Objective: We aim to delineate the progression of cerebellar atrophy (the primary neuroimaging finding) in children with phosphomannomutase-deficiency (PMM2-CDG) by analyzing longitudinal MRI studies and performing cerebellar volumetric analysis and a 2D cerebellar measurement. Methods: Statistical analysis was used to compare MRI measurements [midsagittal vermis relative diameter (MVRD) and volume] of children with PMM2-CDG and sex- and age-matched controls, and to determine the rate of progression of cerebellar atrophy at different ages. Results: Fifty MRI studies of 33 PMM2-CDG patients were used for 2D evaluation, and 19 MRI studies were available for volumetric analysis. Results from a linear regression model showed that patients have a significantly lower MVRD and cerebellar volume compared to controls (p < 0.001 and p < 0.001 respectively). There was a significant negative correlation between age and MVRD for patients (p = 0.014). The rate of cerebellar atrophy measured by the loss of MVRD and cerebellar volume per year was higher at early ages (r = −0.578, p = 0.012 and r = −0.323, p = 0.48 respectively), particularly in patients under 11 years (p = 0.004). There was a significant positive correlation between MVRD and cerebellar volume in PMM2-CDG patients (r = 0.669, p = 0.001). Conclusions: Our study quantifies a progression of cerebellar atrophy in PMM2-CDG patients, particularly during the first decade of life, and suggests a simple and reliable measure, the MVRD, to monitor cerebellar atrophy. Quantitative measurement of MVRD and cerebellar volume are essential for correlation with phenotype and outcome, natural follow-up, and monitoring in view of potential therapies in children with PMM2-CDG.
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U2 - 10.1007/s10545-017-0028-4
DO - 10.1007/s10545-017-0028-4
M3 - Article
C2 - 28341975
AN - SCOPUS:85016178366
SN - 0141-8955
VL - 40
SP - 709
EP - 713
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 5
ER -