Clinical features of Fabry's disease in Australian patients

Background: Anticipating the prospect of specific treatment, we studied a large group of Australians with Fabry's disease. Aims: We aimed to: (i) document the clinical features of Fabry's disease in Australian patients, (ii) test the hypothesis that clinical features vary with specific mutation and blood group and (iii) assess small-fibre peripheral nerve function. Methods: A questionnaire was forwarded to all Australian patients known to us. Patients were invited to attend for clinical, renal cardiac, ophthalmological and neurological assessment. Results: Sixty-seven patients (29 men and 38 women) from 18 families participated. Diagnosis in index cases was delayed by 10 years in nearly all families. Common clinical features are: (i) episodic acroparaesthesia (100% of hemizygotes; 53% of heterozygotes), (ii) anhydrosis (93%; 1%), (iii) characteristic rash (93%; 13%), (iv) renal disease (69%; 21%), (v) ischaemic heart disease (28%; 26%), (vi) palpitations (62%; 29%), (vii) mitral valve murmurs (37%; 23%) and (viii) premature cerebrovascular disease (31%; 5%). Ophthalmic findings of cornea verticillata (96%; 76%) and anterior cataract (48%; 14%) were common. Findings were variable within and between families. In women, anhydrosis reliably predicts the presence of significant Fabry's renal disease. Small nerve fibre testing using quantitative sensory testing was clearly abnormal in 95% of male patients, and in those female patients with paraesthesiae. Conclusions: Symptoms of anhydrosis, acroparaesthesiae, rash and renal disease suggest diagnosis of Fabry's. Women are commonly symptomatic, and the advent of therapy highlights the practical advantage of earlier diagnosis.