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ABeta amyloidosis, Dutch type
Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) is a form of HCHWA (see this term), a group of familial central nervous system disorders, characterized by severe cerebral amyloid angiopathy (CAA), hemorrhagic and non-hemorrhagic strokes and dementia.
ORPHA:100006Classification level: Subtype of disorder
- ABetaE22Q amyloidosis
- HCHWA, Dutch type
- Hereditary cerebral hemorrhage with amyloidosis, Dutch type
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal dominant
- Age of onset: Adult
- ICD-10: E85.4+ I68.0*
- OMIM: 605714
- UMLS: C0268394 C2931672
- MeSH: C537944 D028243
- GARD: -
- MedDRA: -
The prevalence is unknown. It has been seen in three Dutch families, that are most likely related (before 17th century), to date. Approximately 200-300 patients are known to be affected.
HCHWA-D presents with hemorrhagic stroke between the ages of 39-76 years (average age 50 years). In one third of cases, the initial stroke is fatal, recurrent strokes are seen in those who survive and patients often suffer from serious disability. Cognitive decline can be a presenting symptom in some cases but often occurs after the initial or recurrent strokes. Dementia is seen in the majority of patients with HCHWA-D over the age of 40. Epilepsy is also seen in half of patients who have already experienced a previous stroke.
HCHWA-D is due to a mutation in the APP gene on chromosome 21q21.2, encoding the beta-amyloid precursor protein. The mutation leads to extensive amyloid-beta deposition in the meningocortical arterioles, causing them to weaken and rupture.
The diagnosis is clear when a patient presents with a lobar hemorrhage and is known to come from an affected family. Imaging studies show diffuse white matter damage as well as hemorrhages. Genetic testing reveals a mutation in the APP gene.
Differential diagnoses include other conditions that could cause intracerebral hemorrhage such as coagulopathies, vasculitis (see these terms), CNS neoplasms, cerebral vascular malformations, ischemic stroke and antecedent trauma.
Antenatal diagnosis is possible but is rarely performed.
As HCHWA-D is inherited autosomal dominantly, genetic counseling is possible when a family member is diagnosed with the disease. Pre-symptomatic genetic testing is possible.
Management and treatment
There is currently no acute or preventive treatment for HCHWA-D. Symptomatic treatment (with corticosteroids and antiepileptic drugs) can be given. On pragmatic grounds, antihypertensive treatment is recommended for those with mild to moderate hypertension.
The prognosis is poor. HCHWA-D is often fatal, either acutely at first presentation or, on average, 10 years after symptom onset and after multiple strokes.
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