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Orphanet J Rare Dis. 2017 Sep 15;12(1):155. doi: 10.1186/s13023-017-0707-0.

A quantitative assessment of the evolution of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG).

Author information

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.
3
Pediatrics Department, Hospital Garrahan, Buenos Aires, Argentina.
4
Statistics Department, Fundació Sant Joan de Déu, Barcelona, Spain.
5
Pediatric Institute for Genetic Medicine and Rare Diseases, Hospital Sant Joan de Déu, Barcelona, Spain.
6
Pediatric Neurology Department, Hospital Universitario La Paz, Madrid, Spain.
7
Unit of Child Neurology, Department of Pediatrics, Hospital Infantil Universitario Niño Jesús de Madrid, Madrid, Spain.
8
Grup de Recerca en Neurologia Pediàtrica, Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona, Secció de Neurologia Pediàtrica, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
9
Neuropediatric, Radiology and Clinical Biochemistry Departments, Hospital Sant Joan de Déu, Barcelona, Spain. mserrano@hsjdbcn.org.
10
U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Barcelona, Spain. mserrano@hsjdbcn.org.
11
Pediatric Institute for Genetic Medicine and Rare Diseases, Hospital Sant Joan de Déu, Barcelona, Spain. mserrano@hsjdbcn.org.
12
Neurology Department, Hospital Sant Joan de Déu, Passeig Sant Joan de Déu, 2, 08950, Esplugues, Barcelona, Spain. mserrano@hsjdbcn.org.

Abstract

BACKGROUND:

We aim to delineate the progression of cerebellar syndrome in children with phosphomannomutase-deficiency (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 PMM2-CDG 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

PMID:
28915903
PMCID:
PMC5602850
DOI:
10.1186/s13023-017-0707-0
[Indexed for MEDLINE]
Free PMC Article

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