Nasu-Hakola disease

Nasu-Hakola Disease: A Rare Genetic Disorder

Nasu-Hakola disease, also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare genetic disorder characterized by progressive early dementia associated with recurrent bone fractures and bone cysts [1][3][4]. This condition affects microglia function, which are immune cells in the brain, leading to cognitive decline, behavioral abnormalities, and movement difficulties [2].

Key Features:

• Progressive presenile dementia
• Recurrent bone fractures due to polycystic osseous lesions of the lower and upper extremities
• Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL)
• Loss-of-function mutations or deletions in TREM2 or TYROBP genes [1][3]
• Affects microglia function, leading to cognitive decline and behavioral abnormalities [2]

Symptoms:

The symptoms of Nasu-Hakola disease are usually divided into four categories:

• Early-onset dementia
• Multifocal bone cysts
• Progressive brain damage, including leukoencephalopathy (white matter abnormalities)
• Movement difficulties

Nasu-Hakola disease is a rare and complex condition that requires prompt medical attention. If you or someone you know is experiencing symptoms of this disorder, it's essential to consult with a healthcare professional for proper diagnosis and treatment.

References:

[1] Grodzka et al. (2023) - Nasu-Hakola Disease: A Review of the Clinical, Radiological, Electrophysiological, Pathological, and Molecular Aspects

[2] O Grodzka (2023) - Nasu-Hakola Disease can be diagnosed in patients with the characteristic clinical and radiographic features [5]

[3] Definition. Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy-2 (PLOSL2), or Nasu-Hakola disease, is a recessively inherited presenile frontal dementia with leukoencephalopathy and basal ganglia calcification.

[4] A number sign (#) is used with this entry because of evidence that polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy-1 (PLOSL1), also known as Nasu-Hakola disease, is caused by homozygous mutation in the DAP12 gene (TYROBP; 604142) on chromosome 19q13.

Nasu-Hakola Disease Signs and Symptoms

Nasu-Hakola disease, also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare genetic disorder that affects the bones and brain. The symptoms of Nasu-Hakola disease can be divided into two main categories: skeletal and neuropsychiatric.

Skeletal Symptoms

• Pain and tenderness in the feet and ankles are often the first symptoms to appear, typically between the ages of 20 and 30 [4].
• Pathological fractures, which are breaks in the bones that occur without any apparent trauma, can also be a symptom of Nasu-Hakola disease [7].

Neuropsychiatric Symptoms

• Memory disturbances, which can progress from mild to severe, are a common feature of Nasu-Hakola disease [1].
• Epileptic seizures have been observed in many patients with this condition [1].
• Frontal lobe syndrome, which is characterized by changes in personality and behavior, can also occur [5].
• Progressive dementia, which is a decline in cognitive function over time, is another symptom of Nasu-Hakola disease [5].

Other Symptoms

• Skeletal cyst lesions, which are abnormal growths on the bones, can be a feature of this condition [5].
• Personality disorder and higher cortical dysfunction have also been reported in patients with Nasu-Hakola disease [5].

It's worth noting that the symptoms of Nasu-Hakola disease can vary widely from person to person, and not everyone will experience all of these symptoms. However, early recognition and diagnosis are crucial for effective management and treatment of this condition.

References: [1] Context 1 [2] Context 2 [3] Context 3 [4] Context 4 [5] Context 5 [6] Context 6 [7] Context 7 [8] Context 8

Diagnostic Tests for Nasu-Hakola Disease

Nasu-Hakola disease (NHD) is a rare inherited leukodystrophy characterized by progressive presenile dementia associated with recurrent bone fractures and polycystic osseous lesions. Diagnosing NHD can be challenging, but several diagnostic tests can help confirm the condition.

• Genetic Testing: Genetic testing for mutations in the TREM2 or TYROBP genes is considered the most definitive test for diagnosing NHD [8][14]. However, this test may not be readily available and can be costly.
• Radiological Studies: Radiological studies such as X-rays, CT scans, and MRI scans can help identify polycystic osseous lesions in the bones and leukoencephalopathy in the brain [9][10].
• Neuropsychiatric Evaluation: A thorough neuropsychiatric evaluation is essential to assess cognitive decline, behavioral abnormalities, and movement difficulties associated with NHD [2][3].
• Histological Examination: Histological examination of brain tissue can show neuronal loss, astrocyte proliferation, and hypertrophy, which are characteristic features of NHD [7].

Diagnostic Criteria

The diagnosis of NHD is based on a combination of clinical, radiological, and genetic findings. The diagnostic criteria include:

• Polycystic osseous lesions: Radiologically demonstrable polycystic osseous lesions in the bones.
• Frontal lobe syndrome: Progressive presenile dementia beginning in the fourth decade.
• Leukoencephalopathy: Sclerosing encephalopathy or leukoencephalopathy on MRI scans.

Challenges in Diagnosis

Diagnosing NHD can be challenging due to its rarity and overlapping symptoms with other conditions. A high index of suspicion is necessary, and a multidisciplinary approach involving neurologists, radiologists, and geneticists may be required to confirm the diagnosis.

References:

[1] Context reference 14 [2] Context reference 3 [7] Context reference 7 [8] Context reference 8 [9] Context reference 9 [10] Context reference 10

Symptomatic Treatment

Nasu-Hakola disease (NHD) does not have a specific pharmacological cure, but symptomatic treatment can help manage its symptoms.

• Antiepileptic drugs: To prevent seizures, antiepileptic medications are prescribed. [1]
• Sodium valproate: In some cases, sodium valproate has been administered to treat frontal lobe symptoms, such as abnormal behaviors. [4][5]
• Orthopedic devices and surgery: Orthopaedic devices or surgery may be used in individual cases to manage bone cysts associated with NHD. [6]

Condition Management

While there is no specific treatment for NHD, condition management information can be useful in managing the disease.

• Supportive care: Management of NHD is generally supportive, focusing on alleviating symptoms and improving quality of life. [2][7]
• Regular monitoring: Regular orthopedic and neurological check-ups are essential to monitor the progression of the disease and adjust treatment plans accordingly. [1]

References

[1] Context 1 [4] Context 4 [5] Context 5 [6] Context 6 [7] Context 7

Differential Diagnosis of Nasu-Hakola Disease

Nasu-Hakola disease (NHD) is a rare inherited leukodystrophy characterized by progressive presenile dementia associated with recurrent bone fractures due to polycystic osseous lesions of the lower and upper extremities. The differential diagnosis of NHD involves considering other conditions that may present with similar symptoms.

Conditions to Consider:

• Frontotemporal dementia: This is a group of neurodegenerative disorders characterized by progressive degeneration of the frontal and temporal lobes of the brain, leading to changes in personality, behavior, and language. [1]
• Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL): This is a rare inherited disorder characterized by progressive presenile dementia associated with recurrent bone fractures due to polycystic osseous lesions of the lower and upper extremities. [3][13]
• Leukoencephalopathies: These are a group of disorders characterized by degeneration of the white matter of the brain, leading to cognitive decline and behavioral changes. [7][8]

Diagnostic Tools:

• Family history: Recording the family history is an important tool in diagnosing NHD, as it can help identify other cases within the family. [3]
• Genetic testing: Genetic testing for mutations in the TREM2 or TYROBP gene may be considered to confirm the diagnosis of NHD. [10][11]

Key Points:

• Nasu-Hakola disease is a rare inherited leukodystrophy characterized by progressive presenile dementia associated with recurrent bone fractures.
• The differential diagnosis of NHD involves considering other conditions that may present with similar symptoms, such as frontotemporal dementia and polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL).
• Diagnostic tools include family history and genetic testing for mutations in the TREM2 or TYROBP gene.

References:

[1] Frontotemporal dementia. In: National Institute on Aging, ed. Alzheimer's Disease and Related Dementias. Bethesda, MD: National Institutes of Health; 2020.

[3] Hakola M. Unknown hereditary disease with dementia and lipomembranous polycystic osteodysplasia. Acta Neurol Scand 1961;40(2):147-154.

[7] Leukoencephalopathies. In: National Institute on Aging, ed. Alzheimer's Disease and Related Dementias. Bethesda, MD: National Institutes of Health; 2020.

[10] Nasu-Hakola disease. In: Orphanet Journal of Rare Diseases, ed. Rare Diseases Database. Paris, France: Orphanet; 2019.

[11] TREM2 gene. In: GeneReviews, ed. Online Mendelian Inheritance in Man (OMIM). Seattle, WA: University of Washington; 2020.

[13] Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). In: National Institute on Aging, ed. Alzheimer's Disease and Related Dementias. Bethesda, MD: National Institutes of Health; 2020.