CADASIL

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What is CADASIL?

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, usually called CADASIL, is an inherited form of stroke and other impairments. This condition affects small blood vessels, mainly in the brain. An abnormality in the muscle cells surrounding these blood vessels (vascular smooth muscle cells) gradually destroys the blood vessel cells. The resulting blood vessel damage can lead to migraines, emotional and mental disorders, stroke-like episodes, dementia, and other impairments of normal brain function. Patients with CADASIL are also at increased risk of heart attack (myocardial infarction) because of damaged blood vessels in the heart. Most patients with CADASIL do not have the common risk factors for stroke and heart attack, such as high blood pressure and high cholesterol, although in some cases these features may also be present.

How common is CADASIL?

The prevalence of CADASIL is unknown. A Scottish study suggested the prevalence of CADASIL in that population was about 2 in every 100,000 adults. Worldwide, approximately 400 families have been described with this disorder.

What genes are related to CADASIL?

Mutations in the NOTCH3 gene cause CADASIL.

The NOTCH3 gene makes a protein called the Notch3 receptor protein, which plays a role in the development, function and maintenance of vascular smooth muscle cells. Mutations in the NOTCH3 gene lead to an abnormal version of the Notch3 protein that builds up in vascular smooth muscle cells. Accumulation of the abnormal Notch3 protein is thought to cause the degeneration of these muscle cells, leading to the loss of function of blood vessels in the brain and heart.

How do people inherit CADASIL?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder.

In most cases, an affected person has one parent with the condition.

A few rare cases of patients with new mutations in the NOTCH3 gene have been identified.

Source: National Institutes of Health

Studies in the area of hematuria immunology reported from Kyoto Prefectural University, Department of Internal Medicine

"We report here a newly identified CADASIL patient and discuss unique vascular lesions observed in the kidney. A 64-year-old female was admitted to our hospital for the investigation of proteinuria, hematuria and progressive neurological abnormalities. Her mother and brother died of cerebral infarction at a relatively young age despite a lack of apparent risk factors for arteriosclerosis. Over the past 4 months before admission, she had suffered from frequent transient ischemic attacks despite appropriate antiplatelet therapy. Blood examination revealed mild renal insufficiency and urinalysis revealed moderate protein excretion and dysmorphic hematuria. Magnetic resonance imaging of the brain revealed multiple infarcts and leukoencephalopathy. Histopathological analysis of the kidney revealed focal segmental mesangial proliferation, the loss and degeneration of arterial medial smooth muscle cells and arterial intimal thickening. Immunofluorescence analysis of glomeruli revealed IgA deposition in the mesangial area. Electron microscope analysis revealed electron-dense deposition also in the mesangial area. In addition, granular osmophilic material (GOM) was observed in the extraglomerular mesangial area and around the vascular smooth muscle cells. Genetic analysis of Notch3 revealed an R141C missense mutation and she was diagnosed with CADASIL complicated with IgA nephropathy. In immunohistological analysis, Notch3 stains were positive in vascular smooth muscle cells of the interlobular arteries and both afferent and efferent arterioles, and weak in the glomerular mesangial area. Antihypertensive treatment using angiotensin II receptor blocker and a low protein diet were initiated, and her urinary protein excretion decreased to 0.2 g/day. However, due to the progression of her neurological abnormalities, she became socially withdrawn. In CADASIL, GOM, abnormal accumulation of Notch3 ectodomain, is thought to induce the degeneration and loss of vascular smooth muscle cells and subsequent intimal thickening," wrote T. Kusaba and colleagues, Kyoto Prefectural University, Department of Internal Medicine.

The researchers concluded: "Analysis of our cases provided that these morphological abnormalities were also observed in the CADASIL patient kidney."

Kusaba and colleagues published their study in Clinical Nephrology (Renal involvement in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Clinical Nephrology, 2007;67(3):182-7).

Additional information can be obtained by contacting T. Kusaba, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Dept. of Internal Medicine, 456 Kajii-cho Kamigyo-ku Kyoto-city, 602-8566, Japan.

The publisher of the journal Clinical Nephrology can be contacted at: Dustri-Verlag Dr. Karl Feistle, Bahnhofstrasse 9 Postfach 49, D-82032 Deisenhofen-Muenchen, Germany.

Keywords: Japan, Hematuria Immunology, Hematuria, Immunology, Kidney, Nephrology.

This article was prepared by Gastroenterology Week editors from staff and other reports. Copyright 2007, Gastroenterology Week via NewsRx.com.