Nasu-Hakola disease

Last revised by Rohit Sharma on 11 Feb 2021

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.  

Although the exact incidence is not known, the condition is considered to be very rare.

Nasu-Hakola disease is often unrecognised until neuropsychiatric symptoms become apparent, which is typically in early middle age (25-40 years of age) 3. Prior to cognitive decline, patients may have a history of bone cysts and fractures. Later a progressive dementia becomes evident, usually characterized by frontal lobe dysfunction (e.g. disinhibition) as well as myoclonic twitches, gait disturbances and seizures 1.

Nasu-Hakola disease is inherited as an autosomal recessive disorder. Two genes have been identified, each able to result in the Nasu-Hakola disease phenotype: TYROBP and TREM2 genes 1.

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 3.

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 3.

Some patients also demonstrate cerebellar volume loss 3.

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

Progressive dementia usually results in death in the 5th decade of life 2,3.

The condition was first described separately by T Nasu and H P Hakola in the 1970s 4,5.

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