Nasu Disease; Lipomembranous Osteodysplasia with Leukodystrophy; Polycystic Lipomembranous Osteodysplasia with sclerosing leukoencephalopathy (PLOSL)
Inheritance from both parents will result in the disease
Age range at onset:
Adolescent and adult (typically 20-30)
Specialists you may see:
NHD affects the bones and the brain progressively, with symptoms most commonly beginning between the ages of 20 and 30 with pain and tenderness in the feet and ankles. Fractures will become common in the following years, particularly in wrists, hands, ankles and feet as bones become weaker due to cyst-like changes and osteoporosis.
Symptoms relating to the brain usually begin in a person’s thirties, although some experience these before bone-related symptoms. Personality changes are the first noticeable symptom, followed by loss of judgement and inhibition, poor concentration, periods of euphoria and epileptic seizures. Over time, this worsens into a loss of thinking and reasoning abilities and an inability to walk and talk. Those with Nasu-Hakola disease do not usually live past their forties.
Mutations in the TREM2 or TRYOBP gene (also called DAP12) cause Nasu-Hakola disease. Proteins produced by these genes help to replace old bone tissue with new bone, so mutations in the gene cause disruption in bone growth. These proteins also aid immune cells in the brain and spinal cord, although researchers are not yet sure how this leads to progressive neurological symptoms.