Late-onset spastic ataxia phenotype in a patient with a homozygous DDHD2 mutation

Sci Rep. 2014 Nov 24:4:7132. doi: 10.1038/srep07132.

Abstract

Autosomal recessive cerebellar ataxias and autosomal recessive hereditary spastic paraplegias (ARHSPs) are clinically and genetically heterogeneous neurological disorders. Herein we describe Japanese siblings with a midlife-onset, slowly progressive type of cerebellar ataxia and spastic paraplegia, without intellectual disability. Using whole exome sequencing, we identified a homozygous missense mutation in DDHD2, whose mutations were recently identified as the cause of early-onset ARHSP with intellectual disability. Brain MRI of the patient showed a thin corpus callosum. Cerebral proton magnetic resonance spectroscopy revealed an abnormal lipid peak in the basal ganglia, which has been reported as the hallmark of DDHD2-related ARHSP (SPG 54). The mutation caused a marked reduction of phospholipase A1 activity, supporting that this mutation is the cause of SPG54. Our cases indicate that the possibility of SPG54 should also be considered when patients show a combination of adult-onset spastic ataxia and a thin corpus callosum. Magnetic resonance spectroscopy may be helpful in the differential diagnosis of patients with spastic ataxia phenotype.

Publication types

  • Case Reports

MeSH terms

  • Age of Onset
  • Aged
  • Brain / diagnostic imaging
  • Female
  • Gene Frequency
  • Homozygote
  • Humans
  • Intellectual Disability / epidemiology*
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Magnetic Resonance Imaging
  • Middle Aged
  • Muscle Spasticity / epidemiology*
  • Muscle Spasticity / genetics*
  • Muscle Spasticity / pathology
  • Mutation, Missense
  • Optic Atrophy / epidemiology*
  • Optic Atrophy / genetics*
  • Optic Atrophy / pathology
  • Pedigree
  • Phenotype
  • Phospholipases / chemistry
  • Phospholipases / genetics*
  • Polymorphism, Single Nucleotide
  • Protein Structure, Tertiary
  • Radiography
  • Sequence Analysis, DNA
  • Spinocerebellar Ataxias / epidemiology*
  • Spinocerebellar Ataxias / genetics*
  • Spinocerebellar Ataxias / pathology

Substances

  • Phospholipases
  • DDHD2 protein, human

Supplementary concepts

  • Spastic Ataxia