Cerebrovascular complications of Fabry's disease

Abstract

Fabry's disease (FD) is a rare, sex‐linked disorder resulting from α‐galactosidase deficiency. Cerebrovascular complications have been reported in the literature but have not been systematically analyzed. We report 2 patients and review 51 previously reported cases (descriptive meta‐analysis) to clarify the clinical, radiologic, and pathologic features. The average age at onset of cerebrovascular symptoms was 33.8 years for hemizygous individuals (n = 43) and 40.3 years of heterozygotes (n = 10). The most frequent symptoms and signs were as follows (in descending order of frequency): hemiparesis, vertigo/dizziness, diplopia, dysarthria, nystagmus, nausea/vomiting, head pain, hemiataxia, and ataxia of gait, in the hemizygote group; and memory loss, dizziness, ataxia, hemiparesis, loss of consciousness and hemisensory symptoms, in the heterozygote group. The vertebrobasilar circulation was symptomatic in 67% of the hemizygotes and 60% of the heterozygotes. Intracerebral hemorrhage was found in 4 patients (3 hemizygotes and 1 heterozygote). Elongated, ectatic, tortuous vertebral and basilar arteries were the most common angiographic and pathologic features. For the hemizygotes, the recurrence rate for cerebrovascular disease was 76% and the death rate was 55%; 86% of the heterozygotes had recurrent cerebrovascular event(s) and 40% died. The cerebrovascular manifestations of FD, in both hemizygotes and heterozygotes, are predominantly due to dilative arteriopathy of the vertebrobasilar circulation, frequently recur, and portend a poor prognosis.