General description

Nasu-Hakola disease, also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, is an autosomal recessive disorder caused by mutations in the DAP12 (TYROBP) or TREM2 genes. It is characterized by the combination of multiple bone cysts leading to pathological fractures and early-onset dementia due to white matter degeneration. The disease is more common in Japan and Finland.

Disease Progression

1. Asymptomatic phase (up to the 20s): No apparent symptoms.
2. Bone symptom phase (after the 20s): Multiple bone cysts, particularly in the long bones, leading to pathological fractures, often in the wrists and ankles.
3. Early neuropsychiatric symptom phase (after the 30s): Frontal lobe symptoms such as disinhibition, euphoria, personality changes, speech difficulties, and psychiatric symptoms, as well as seizures.
4. Late neuropsychiatric symptom phase (after the 40s): Progressive dementia, leading to immobility and, ultimately, death, often due to complications like aspiration pneumonia.

Radiographic features

Imaging studies reveal generalized cerebral atrophy, with ventriculomegaly and enlarged sulci, gradually progressing from adolescence to middle age. CT and T2WI on MRI show hyperattenuation and hypointensity in the basal ganglia, reflecting calcification. T2WI and FLAIR demonstrate diffuse hyperintensity in the white matter.