Clinical and neuroimaging features of autosomal recessive spastic paraplegia 35 (SPG35): case reports, new mutations, and brief literature review

Neurogenetics. 2018 May;19(2):123-130. doi: 10.1007/s10048-018-0538-8. Epub 2018 Feb 8.


Spastic paraplegia 35 (SPG35) is a recessive condition characterized by childhood onset, progressive course, complicated by dystonia, dysarthria, cognitive impairment, and epilepsy. Mutations in the FA2H gene have been described in several families, leading to the proposal of a single entity, named fatty acid hydrolase-associated neurodegeneration (FAHN). Several reports have described a polymorphic radiological picture with white matter lesions of various degrees and a distinct form of neurodegeneration with brain iron accumulation. While we reviewed the pertinent literature, we also report three new patients with SPG35, highlighting the possible absence of white matter lesions even after a long neuroimaging follow-up. Three-dimensional modeling of the mutated proteins was helpful to elucidate the role of the site of mutations and the correlation with the residual enzyme activity as determined in cultured skin fibroblasts.

Keywords: Complicated hereditary spastic paraplegia; FA2H; SPG35.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Brain / diagnostic imaging
  • Brain / pathology
  • Child
  • Female
  • Genetic Association Studies
  • Humans
  • Magnetic Resonance Imaging
  • Mixed Function Oxygenases / chemistry
  • Mixed Function Oxygenases / genetics*
  • Mutation, Missense
  • Protein Structure, Tertiary
  • Spastic Paraplegia, Hereditary / diagnostic imaging*
  • Spastic Paraplegia, Hereditary / genetics*
  • Spastic Paraplegia, Hereditary / pathology


  • Mixed Function Oxygenases
  • fatty acid alpha-hydroxylase

Supplementary concepts

  • Spastic paraplegia type 5A, recessive