Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), also known as Nasu-Hakola disease, is a rare genetic disorder characterized by a combination of progressive presenile dementia and recurrent bone fractures due to bone cysts.

Overview

The disease was initially described in the 1970s in separate reports from Japan by Nasu and from Finland by Hakola, hence its eponymous name. It is a hereditary condition and affects both the central nervous system and the skeletal system.

Symptoms and Clinical Features

Neurological

• Onset of neuropsychiatric symptoms in the 3rd to 5th decade of life
• Progressive presenile dementia
• Personality changes, irritability, and mood disturbances
• Seizures
• Motor symptoms such as rigidity and tremors

Skeletal

• Bone pain and tenderness
• Bone cysts leading to spontaneous fractures, especially in the wrists and ankles
• Radiological evidence showing osteoporosis and polycystic bone lesions

Genetics

Nasu-Hakola disease is inherited in an autosomal recessive manner. It has been linked to mutations in two genes: TREM2 (triggering receptor expressed on myeloid cells 2) and DAP12 (DNAX activation protein 12). Both these genes play vital roles in the functioning of microglial cells in the brain and osteoclasts in the bones.

Diagnosis

The diagnosis of Nasu-Hakola disease involves:

• Clinical evaluation and history taking
• Neuroimaging (MRI) which might reveal white matter changes and atrophy
• Bone X-rays to identify cystic lesions
• Genetic testing to confirm mutations in TREM2 or DAP12

Treatment

There is no specific treatment for Nasu-Hakola disease. Management focuses on:

• Symptomatic relief
• Physiotherapy and orthopedic interventions for bone-related issues
• Neuropsychiatric support and care for cognitive decline

Epidemiology

The condition is extremely rare with higher prevalence noted in Japan and Finland. However, cases have been reported globally.

Prognosis

The disease typically progresses over 10 to 15 years from the onset of symptoms. Most patients become severely debilitated, requiring full-time care, and life expectancy is reduced.

See Also

• Genetic Disorders
• Dementia
• Bone disorders

NIH genetic and rare disease info

• NIH info on Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy is a rare disease.