Longitudinal volumetric and 2D assessment of cerebellar atrophy in a large cohort of children with phosphomannomutase deficiency (PMM2-CDG).
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.



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.



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).



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.
Neuropediatric, Radiology and Clinical Biochemistry Departments, Hospital Sant Joan de Déu, Barcelona, Spain.|U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Barcelona, Spain.
Víctor
V
de Diego
Genetic Medicine and Rare Diseases' Pediatric Institute, Hospital Sant Joan de Déu, Barcelona, Spain.
Antonio F
AF
Martínez-Monseny
Neuropediatric, Radiology and Clinical Biochemistry Departments, Hospital Sant Joan de Déu, Barcelona, Spain.|U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Barcelona, Spain.
Jordi
J
Muchart
Statistics Department, Fundació Sant Joan de Déu, Barcelona, Spain.
Daniel
D
Cuadras
Neuropediatric, Radiology and Clinical Biochemistry Departments, Hospital Sant Joan de Déu, Barcelona, Spain.|U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Barcelona, Spain.
Raquel
R
Montero
Neuropediatric, Radiology and Clinical Biochemistry Departments, Hospital Sant Joan de Déu, Barcelona, Spain.|U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Barcelona, Spain.
Rafael
R
Artuch
Centro de Diagnóstico de Enfermedades Moleculares (CEDEM), Universidad Autónoma de Madrid (UAM), U-746 Centre for Biomedical Research on Rare Diseases (CIBER-ER) Madrid, Instituto de Salud Carlos III, IdiPAZ, Madrid, Spain.
Celia
C
Pérez-Cerdá
Centro de Diagnóstico de Enfermedades Moleculares (CEDEM), Universidad Autónoma de Madrid (UAM), U-746 Centre for Biomedical Research on Rare Diseases (CIBER-ER) Madrid, Instituto de Salud Carlos III, IdiPAZ, Madrid, Spain.
Belén
B
Pérez
Neuropediatric, Radiology and Clinical Biochemistry Departments, Hospital Sant Joan de Déu, Barcelona, Spain.|U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Barcelona, Spain.
Belén
B
Pérez-Dueñas
Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MA, USA.
Andrea
A
Poretti
Neuropediatric, Radiology and Clinical Biochemistry Departments, Hospital Sant Joan de Déu, Barcelona, Spain. mserrano@hsjdbcn.org.|U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Barcelona, Spain. mserrano@hsjdbcn.org.|Genetic Medicine and Rare Diseases' Pediatric Institute, Hospital Sant Joan de Déu, Barcelona, Spain. mserrano@hsjdbcn.org.|Neurology Department & Genetic Medicine, Hospital Sant Joan de Déu, and U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Passeig Sant Joan de Déu, 2, 08950, Esplugues, Barcelona, Spain. mserrano@hsjdbcn.org.
Mercedes
M
Serrano
D001284:Atrophy / Q000378:metabolism* / Q000473:pathology*; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D017875:Phosphotransferases (Phosphomutases) / Q000172:deficiency* / Q000378:metabolism*
D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase
Cerebellar Atrophy; Cerebellar Volume; Focal Epilepsy; Spinocerebellar Ataxia; Volumetric Analysis