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Fabry disease: Clinical features, diagnosis, and management of cardiac disease

Sherif F Nagueh, MD, FACC, FAHA, FASE
Section Editor
William J McKenna, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC


Fabry disease (MIM 300644, also known as angiokeratoma corporis diffusum, ceramide trihexosidosis, or Anderson-Fabry disease) is an X-linked glycolipid storage disease [1,2]. It is caused by deficient activity of the lysosomal enzyme alpha-galactosidase A, resulting in the accumulation of globotriaosylceramide in lysosomes in multiple cell types throughout the body.

While males are more severely diseased, most heterozygous females are also affected, though usually at a later age [3-6].

Clinical manifestations are variable and include cutaneous, corneal, cardiac, renal, and neurologic manifestations. The typical presentation occurs in children who suffer from peripheral neuropathy of the hands and feet, nausea, and abdominal pain. However, diagnosis is frequently missed due to the rarity of the disease. Other characteristic features include reduced sweating and the cutaneous lesions of angiokeratoma corporis (picture 1 and picture 2), which are vascular papules typically distributed in the inguinal, hip, and periumbilical areas. These become more prominent with age. Manifestations of renal disease include proteinuria and progressive renal insufficiency, which sometimes result in end-stage renal disease. In adults, there is progressive cardiac, renal, and cerebral involvement (transient ischemic attacks and strokes), which are the major causes of death associated with Fabry disease. (See "Clinical features and diagnosis of Fabry disease".)

The cardiac features of Fabry disease and the incidence of unexpected Fabry disease in patients with otherwise unexplained left ventricular hypertrophy will be reviewed here. The general clinical manifestations and treatment of Fabry disease are discussed separately. (See "Clinical features and diagnosis of Fabry disease" and "Fabry disease: Treatment".)


Clinical features — Cardiovascular manifestations of Fabry disease include left ventricular hypertrophy (LVH), aortic and mitral regurgitation, conduction defects, coronary artery disease, hypertension, and aortic root dilation [6-11]. The right ventricle is also often hypertrophied [12]. Many patients with cardiac involvement are asymptomatic, whereas others present with angina, dyspnea, palpitations, or syncope. Rare patients have advanced heart failure symptoms in the setting of unexplained LVH and generally normal LV ejection fraction (LVEF).

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Literature review current through: Nov 2017. | This topic last updated: Jul 07, 2016.
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