Fabry's Disease

Fabry's disease is an X-linked inborn error of globotriaosylceramide metabolism secondary to deficient lysosomal -galactosidase A activity, resulting in excessive intracellular storage of globotriaosylceramide.

Affected organs include the vascular endothelium, heart, brain, and kidneys. Classically, Fabry's disease presents in childhood in males with multi-organ involvement. Hemizygotes with hypomorphic mutations sometimes present in the fourth to sixth decade with single organ involvement. Rarely, dominant-negative -galactosidase A mutations or female heterozygotes with unfavorable X inactivation present with mild single-organ involvement.

 Renal biopsy reveals enlarged glomerular visceral epithelial cells packed with small clear vacuoles containing globotriaosylceramide; vacuoles may also be found in parietal and tubular epithelia . These vacuoles of electron-dense materials in parallel arrays (zebra bodies) are easily seen on electron microscopy. Ultimately, glomeruli develop FSGS. The nephropathy of Fabry's disease typically presents in the third decade as mild to moderate proteinuria, sometimes with microscopic hematuria or nephrotic syndrome. Urinalysis may reveal oval fat bodies and birefringent glycolipid globules under polarized light (Maltese cross). Renal biopsy is necessary for definitive diagnosis. Progression to renal failure occurs by the fourth or fifth decade.

 Treatment with recombinant -galactosidase A has been demonstrated to clear microvascular endothelial deposits of globotriaosylceramide from the kidneys, heart, and skin.

Mne: Lyso (young boy) is riding to the gal-a on a zebra wearing a fabric printed with focal segments of three bowls of ceramic around a maltese cross.