Expanding the clinical and genetic heterogeneity of SPAX5

Ann Clin Transl Neurol. 2020 Apr;7(4):595-601. doi: 10.1002/acn3.51024. Epub 2020 Apr 1.


Mutations in the ATPase family 3-like gene (AFG3L2) have been linked to autosomal-dominant spinocerebellar ataxia type 28 and autosomal recessive spastic ataxia-neuropathy syndrome. Here, we describe the case of a child carrying bi-allelic mutations in AFG3L2 and presenting with ictal paroxysmal episodes associated with neuroimaging suggestive of basal ganglia involvement. Studies in skin fibroblasts showed a significant reduction of AFG3L2 expression. The relatively mild clinical presentation and the benign course, in spite of severe neuroimaging features, distinguish this case from data reported in the literature, and therefore expand the spectrum of neurological and neuroradiological features associated with AFG3L2 mutations.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Dependent Proteases / genetics*
  • ATPases Associated with Diverse Cellular Activities / genetics*
  • Child
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Spinocerebellar Ataxias / congenital*
  • Spinocerebellar Ataxias / diagnosis
  • Spinocerebellar Ataxias / genetics
  • Spinocerebellar Ataxias / pathology
  • Spinocerebellar Ataxias / physiopathology


  • ATP-Dependent Proteases
  • AFG3L2 protein, human
  • ATPases Associated with Diverse Cellular Activities

Supplementary concepts

  • Spinocerebellar ataxia 28

Grants and funding

This work was funded by Italian Ministry of Health grant Ricerca Corrente 5X1000.