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CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts

J Paloneva1, T Autti, R Raininko

  • 1Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.

Neurology
|June 13, 2001
PubMed

Insights

Nasu-Hakola disease (PLOSL) involves bone cysts and dementia, often starting with limb pain. Early basal ganglia changes are key, even before dementia symptoms appear.

Area of Science:

  • Neurology
  • Genetics
  • Pathology

Background:

  • Nasu-Hakola disease (PLOSL) is a rare genetic disorder.
  • It presents with bone cysts and progressive dementia.

Purpose of the Study:

  • To analyze neurologic, neuroradiologic, and neuropathologic features of PLOSL patients.
  • Confirm diagnoses using molecular genetic methods.

Main Methods:

  • Analysis of clinical, neurophysiologic, and imaging data from eight PLOSL patients.
  • Autopsy examination of three patients.
  • Genetic analysis revealed DAP12 gene mutations in all patients.

Main Results:

  • Disease onset typically in the third decade with bone pain and fractures.
  • Dementia and frontal lobe syndrome develop by age 30, leading to death by age 40.
  • Neuroimaging shows early basal ganglia calcifications and white matter changes.

Conclusions:

  • PLOSL can manifest neurologically before bone symptoms.
  • Patients with unexplained dementia should be screened for bone abnormalities.
  • Early basal ganglia involvement is characteristic of PLOSL.
Abstract

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