Nasu Hakola disease

Nasu Hakola disease, also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, is a rare inherited neuropsychiatric disorder which in addition to cognitive impairment also demonstrates bone cysts.


Nasu Hakola disease is inherited as an autosomal recessive trait and is often unrecognised until neuropsychiatric symptoms become apparent, which is typically in early middle age (25-40 years of age) . Prior to cognitive decline, patients often have experienced bone pain and fractures, typically from early adulthood .

Clinical presentation

Patients often have a history of bone cysts and fractures, before neuropsychiatric features become evident. Later a progressive dementia becomes evident, usually characterized by frontal lobe dysfunction (e.g. disinhibition) as well as myoclonic twitches, gait disturbances and convulsions .


Two genes have been identified, each able to result in the Nasu Hakola disease phenotype: TYROBP and TREM2 genes .

Radiographic features

Imaging features are non-specific. Generalized cerebral atrophy with ex-vacuo dilatation of the ventricles and sulci is usually present, which progresses with the disease. This is associated with high T2 signal in the subcortical and deep white matter .

Basal ganglia are also involved with calcification, typically the putamina, and loss of volume in the caudate heads, resulting in increased intercaudate distance to inner table width ratio .

Some patients also demonstrate cerebellar volume loss .

Treatment and prognosis

Currently, no specific therapeutic options exist, with management being targeted at dominant clinical symptoms.

Progressive dementia usually results in death in the 5 decade of life .