Neuropsychological tests and functional nuclear neuroimaging provide evidence of subclinical impairment in Nasu-Hakola disease heterozygotes.

Nasu-Hakola disease is a rare, recessively inherited disease characterized by presenile dementia and bone cysts. Until now, no evidence of subclincal pathological changes in individuals heterozygous for the mutations underlying Nasu-Hakola disease has been reported. We performed a functional neuroimaging (99mTc-ECD SPECT) and neuropsychological study of healthy members of an Italian family carrying a mutation in the TREM2 gene. Two healthy subjects heterozygous for one mutated TREM2 allele showed a deficit of visuospatial memory associated with hypoperfusion in the basal ganglia, whereas the homozygotes for the wild-type allele of TREM2 did not show any abnormalities.