How does Fabry disease mimic fibromyalgia?
Most patients with hereditary LSDs present and are diagnosed during childhood. However, female heterozygotes and atypical variants of Fabry disease may have a milder and later-onset phenotype. Fabry disease is an X-linked lipid storage disease caused by deficiency of lysosomal α-galactosidase A (α-Gal A) allowing glycosphingolipids to accumulate in lysosomes. The disease has an incidence of 1 in 40,000 males but can be as high as 1 in 3100 live births if mild forms in both males and females are included. Males with classical Fabry disease usually develop neuromuscular symptoms in childhood including painful crises with burning paresthesias of distal extremities, often accompanied by fever. Female heterozygotes and males with low residual α-Gal A levels may develop disease manifestations for the first time as adults. Neuromuscular manifestations can range from painful acroparesthesias to fibromyalgia. Progressive or isolated cardiac, cerebrovascular, and renal disease can develop later. Diagnosis of Fabry disease should be suspected in any patient with a paternal family history of early-onset renal failure. Patients should be examined for characteristic ocular stigmata (cornea verticillata) and dermal signs (angiokeratomas) . The diagnosis is confirmed in males by determining α-Gal A activity in plasma or peripheral leukocytes. By contrast, female carriers must be tested for one of the specific gene mutations. Early diagnosis is important because enzyme replacement therapy with agalsidase alpha (Replagal) or beta (Fabrazyme) can prevent irreversible organ damage. Recently, migalastat (Galafold) is an oral medication approved to treat Fabry disease. It is a chaperone molecule that binds to the active site of deficient α-Gal A proteins, stabilizes the enzyme, and allows it to traffic into the lysosome where it metabolizes the accumulated glycosphingolipids. The annual cost of oral or infused therapies is about $300,000.
