Clinical and radiological correlates of activities of daily living in cerebellar atrophy caused by PMM2 mutations (PMM2-CDG)

Fabio Pettinato, Giovanni Mostile, Roberta Battini, Diego Martinelli, Annalisa Madeo, Elisa Biamino, Daniele Frattini, Domenico Garozzo, Serena Gasperini, Rossella Parini, Fabio Sirchia, Giuseppe Sortino, Luisa Sturiale, Gert Matthijs, Amelia Morrone, Maja Di Rocco, Renata Rizzo, Jaak Jaeken, Agata Fiumara, Rita Barone

Research output: Contribution to journalArticlepeer-review

Abstract

We aimed to identify clinical, molecular and radiological correlates of activities of daily living (ADL) in patients with cerebellar atrophy caused by PMM2 mutations (PMM2-CDG), the most frequent congenital disorder of glycosylation. Twenty-six PMM2-CDG patients (12 males; mean age 13 ± 11.1 years) underwent a standardized assessment to measure ADL, ataxia (brief ataxia rating scale, BARS) and phenotype severity (Nijmegen CDG rating scale, NCRS). MRI biometry of the cerebellum and the brainstem were performed in 23 patients (11 males; aged 5 months–18 years) and 19 control subjects with equal gender and age distributions. The average total ADL score was 15.3 ± 8.5 (range 3–32 out of 36 indicating severe functional disability), representing variable functional outcome in PMM2-CDG patients. Total ADL scores were significantly correlated with NCRS (r2 = 0.55, p < 0.001) and BARS scores (r2 = 0.764; p < 0.001). Severe intellectual disability, peripheral neuropathy, and severe PMM2 variants were all significantly associated with worse functional outcome. Higher ADL scores were significantly associated with decreased diameters of cerebellar vermis (r2 = 0.347; p = 0.004), hemispheres (r2 = 0.436; p = 0.005), and brainstem, particularly the mid-pons (r2 = 0.64; p < 0.001) representing the major radiological predictor of functional disability score in multivariate regression analysis. We show that cerebellar syndrome severity, cognitive level, peripheral neuropathy, and genotype correlate with ADL used to quantify disease-related deficits in PMM2-CDG. Brainstem involvement should be regarded among functional outcome predictors in patients with cerebellar atrophy caused by PMM2-CDG.

Original languageEnglish
Pages (from-to)596-605
Number of pages10
JournalCerebellum
Volume20
Issue number4
DOIs
Publication statusPublished - Aug 2021

Keywords

  • Activities of daily living
  • Ataxia
  • Cerebellar atrophy
  • Congenital disorder(s) of glycosylation
  • PMM2 variants
  • Pons atrophy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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