Alexander disease evolution over time: data from an Italian cohort of pediatric-onset patients: Molecular Genetics and Metabolism

E. Mura, F. Nicita, S. Masnada, R. Battini, C. Ticci, M. Montomoli, A. Berardinelli, C. Pantaleoni, A. Ardissone, T. Foiadelli, E. Tartara, E. Salsano, P. Veggiotti, I. Ceccherini, I. Moroni, E. Bertini, D. Tonduti

Research output: Contribution to journalArticlepeer-review


Alexander disease (AxD) is a leukodystrophy that primarily affects astrocytes and is caused by dominant variants in the Glial Fibrillary Acidic Protein gene. Three main classifications are currently used, the traditional one defined by the age of onset, and two more recent ones based on both clinical features at onset and brain MRI findings. In this study, we retrospectively included patients with genetically confirmed pediatric-onset AxD. Twenty-one Italian patients were enrolled, and we revised all their clinical and radiological data. Participants were divided according to the current classification systems. We qualitatively analyzed data on neurodevelopment and neurologic decline in order to identify the possible trajectories of the evolution of the disease over time. One patient suffered from a Neonatal presentation and showed a rapidly evolving course which led to death within the second year of life (Type Ia). 16 patients suffered from the Infantile presentation: 5 of them (here defined Type Ib) presented developmental delay and began to deteriorate by the age of 5. A second group (Type Ic) included patients who presented a delay in neuromotor development and started deteriorating after 6 years of age. A third group (Type Id) included patients who presented developmental delay and remained clinically stable beyond adolescence. In 4 patients, the age at last evaluation made it not possible to ascertain whether they belonged to Type Ic or Id, as they were too young to evaluate their neurologic decline. 4 patients suffered from the Juvenile presentation: they had normal neuromotor development with no or only mild cognitive impairment; the subsequent clinical evolution was similar to Type Ic AxD in 2 patients, to Id group in the other 2. In conclusion, our results confirm previously described findings about clinical features at onset; based on follow-up data we might classify patients with Type I AxD into four subgroups (Ia, Ib, Ic, Id). Further studies will be needed to confirm our results and to better highlight the existence of clinical and neuroradiological prognostic factors able to predict disease progression. © 2021 Elsevier Inc.
Original languageEnglish
Pages (from-to)353-358
Number of pages6
JournalMol. Genet. Metab.
Issue number4
Publication statusPublished - 2021


  • Alexander disease
  • astrocytopathy
  • GFAP
  • leukodystrophy


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