The renal biopsy diagnosis in this patient was extremely useful for prognostication, genetic counseling and directing clinical management. Although specific therapies for Fabry disease remain ineffective and/or experimental, at least the patient will not be subjected to unnecessary steroid therapy for presumed other glomerulopathies. Renal transplantation is effective for ESRD in patients with Fabry disease because a normal donor kidney has normal levels of alpha- galactosidase A. Renal allografts, however, apparently do not provide enough of the missing enzyme to correct the systemic disease.
Fabry disease is an X-linked disorder that has very high penetrance in male hemizygotes but is usually asymptomatic in heterozygous females. Clinical manifestations include angiokeratomas, palmar erythema, conjunctival telangiectasia, painful neuropathy with paresthesias, hypohidrosis, corneal and lenticular opacity, cardiac dysfunction, and abnormal intestinal mobility causing abdominal pain and diarrhea; as well as renal dysfunction.
Prior to dialysis and renal transplantation, renal failure was the leading cause of death in Fabry disease. Renal dysfunction usually begins insidiously with mild proteinuria and hematuria in about the third decade of life, which often progresses to ESRD within 10 to 20 years.
The distinctive pathologic changes result from accumulation of trihexoside in cells. In the kidney, the resultant vacuolation of cells seen by light microscopy is most conspicuous in glomerular and tubular epithelial cells, but vacuolation also occurs in vessels. The ultrastructural appearance of the myelin figures combined with their extent and distribution is almost pathognomonic for Fabry disease, although the sine qua non is the biochemical defect. Similar intracellular myelin figures occur in kidneys secondary to certain drug exposures, e.g. aminoglycosides and chloroquine, but the number and distribution are quite different. Silicone nephropathy is a rare pathologic differential consideration (Am J Nephrol 3:279-284,1983). Other metabolic storage diseases can mimic Fabry disease at the light microscopic level, but the ultrastructure and of course the biochemistry are different.
2. Farge D, Nadler S, Wolfe LS, et al: Diagnostic value of kidney biopsy in heterozygous Fabry's disease. Arch Pathol Lab Med 109:85-88, 1985
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