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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.
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.
History and etymology
The condition was first described separately by T Nasu and H P Hakola in the 1970s 4,5.
- 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
- 4. Hakola HP, Järvi OH, Sourander P. Osteodysplasia polycystica hereditaria combined with sclerosing leucoencephalopathy, a new entity of the dementia praesenilis group. (1970) Acta neurologica Scandinavica. doi: - Pubmed
- 5. Nasu T, Tsukahara Y, Terayama K. A lipid metabolic disease-"membranous lipodystrophy"-an autopsy case demonstrating numerous peculiar membrane-structures composed of compound lipid in bone and bone marrow and various adipose tissues. (1973) Acta pathologica japonica. doi:10.1111/j.1440-1827.1973.tb01223.x - Pubmed