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Nasa-Hakola Disease Overview

written by: bjlbyron•edited by: lrohner•updated: 6/27/2011

Nasa-Hakola disease is a rare genetic condition that devastates the brain and skeletal system and almost always leads to premature death. Read on to learn more about this troubling disorder and its underlying genetic causes.

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    What Is Nasa-Hakola Disease?

    Nasa-Hakola disease (NHD), or what is also frequently referred to as polycistic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, is a genetic disorder that affects the brain and the skeletal system. Specifically, those who have NHD typically suffer from cyst-like bone defects, or polycistic lipomembranous osteodysplasia, and certain brain problems due to sclerosing leukoencephalopathy.

    NHD symptoms often manifest in affected individuals shortly after they reach adulthood. Many NHD sufferers experience foot and ankle pain as a first symptom, but then become prone to breaking bones due to bone thinning problems as their NHD progresses. Over time, such affected individuals may even lose the ability to walk or grasp objects.

    Later-arising symptoms which may appear about a decade or so after the aforementioned bone symptoms first appear affect brain function. Specifically, NHD-affected individuals may develop one or more of the following:

    • Sudden and drastic change in personality
    • Unusually poor judgment
    • Frequent manic and euphoric feelings
    • Inability to concentrate or think clearly
    • Dementia

    Unfortunately, people who have NHD usually decline relatively quickly after their symptoms first arise. In fact, most of these individuals pass away due to their NHD symptoms between age 30 and age 50. It should be noted, however, that NHD is very rare and that NHD is most commonly seen in the Finnish and Japanese populations. It is estimated that 1 in every 500,000 to one million Finns suffers from NHD.

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    What Is Known About The Genetic Cause of Nasa-Hakola Disease?

    Molecular geneticists have discovered that mutations in either one of two genes, which are designated TREM2 and TYROBP, can cause NHD. The proteins that are encoded by each one of these genes work in conjunction with one another to carry out a yet-to-be-determined function in osteaoblast cells (osteoblast cells serve to break down old, defective bone tissue so that it can be replaced with new bone tissue). Further, the proteins encoded by the TREM2 and TYROBP genes are active and necessary in microglial cells, which are present in both the brain and spinal cord and which help to provide immune protection to these parts of the body. As in the case with osteoblast cells, the important role (or roles) that either of these proteins plays in microglial cells remains unknown.

    People who have one or more mutations in both copies of either one of their TREM2 gene or TYROBP gene are unable to make TREM2 or TYROBP protein at all, or they make only defective copies of one of these proteins. In either case, the result is the same: the osteoblasts and microglial cells of these affected individuals do not function properly, and this improper functioning prevents these cells from helping the body to maintain bone structure and to perform normal brain activities, respectively.

    Although there is no known cure or even an optimal treatment for NHD, it is hoped that further understanding of its genetic causes will lead to the development of a cure or at least a sufficient treatment option. If you are interested in learning more about this rare genetic condition, please consult with your doctor. This article is meant only to provide some basic information about Nasu-Hakola disease, and it is not meant to replace the good advice of your health care provider.

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    References

    Genetics Home Reference, National Institutes of Health, Polycistic lipomembranous osteodysplasia with sclerosing leukoencephalopathy: http://ghr.nlm.nih.gov/condition/polycystic-lipomembranous-osteodysplasia-with-sclerosing-leukoencephalopathy

    J. Paloneva et al., Gene Reviews, University of Washington, Polycistic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL): http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=plosl