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 is 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) 3. Prior to cognitive decline, patients often have experienced bone pain and fractures, typically from early adulthood 3.
Patients often have a history of bone cysts and fractures, before neuropsychiatric features become evident. Later a progressive dementia becomes evident, usually characterised by frontal lobe dysfunction (e.g. disinhibition) as well myoclonic twitches, gait disturbances and convulsions 1.
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. Generalised 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.
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 5th decade of life 2-3.
- 1. Yamazaki K, Yoshino Y, Mori Y et-al. A Case of Nasu-Hakola Disease without Fractures or Consanguinity Diagnosed Using Exome Sequencing and Treated with Sodium Valproate. Clin Psychopharmacol Neurosci. 2015;13 (3): 324-6. doi:10.9758/cpn.2015.13.3.324 - Free text at pubmed - Pubmed citation
- 2. Bianchin MM, Capella HM, Chaves DL et-al. Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy-PLOSL): a dementia associated with bone cystic lesions. From clinical to genetic and molecular aspects. Cell. Mol. Neurobiol. 2004;24 (1): 1-24. Pubmed citation
- 3. Paloneva J, Autti T, Raininko R et-al. CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts. Neurology. 2001;56 (11): 1552-8. Pubmed citation