Nasu-Hakola disease has been reported in approximately 200 cases worldwide and is a rare form of leukodystrophy characterized by progressive pre-senile dementia, frontal lobe syndrome, and repeated fractures of the upper and lower extremities due to polycystic bone lesions.
There are four stages of disease progression: latent, osseus, early neurological, and late neurological phases.
After normal development during childhood (latent phase), the osseous phase begins in adolescence or young adulthood (typically between 20 and 30 years of age) with pain in the hands and feet, as well as repeated fractures of the limbs due to polycystic and osteoporotic bone lesions.
During the third or fourth decade, the early neurological phase sets in, where the patient is subject to personality change typical for the frontal lobe syndrome (lack of concentration, euphoria and loss of judgment and social inhibition). Also, epileptic seizures and initially mild, but later progressive memory disorders can be observed at this stage.
The subsequent late neurological phase brings with it a serious dementia. Patients at this stage usually can no longer talk or move and die at around age 50.
The disease is due to mutations in either the TYROBP gene or the TREM2 gene which encode the tyrosine kinase-binding adapter protein or receptor. Inheritance is autosomal recessive.
The diagnosis is based on clinical and radiological findings. In conventional radiographs, multifocal cystic lesions are found on the bones and skull CT / MRI shows accentuated atrophy of the white matter and typical bilateral calcification of the basal ganglia. A curative therapy does not exist.