Case reportFabry disease: renal involvement limited to podocyte pathology and proteinuria in a septuagenarian cardiac variant. Pathologic and therapeutic implications
Section snippets
Case report
The proband was a 75-year-old man of German descent who had a history of hypertension, hypercholesterolemia, and a myocardial infarction. At age 65, he had a urinary protein level of 0.3 g/L. Five months before examination, he had dyspnea upon exertion. His ventricular ejection fraction had decreased markedly from low normal to 35% and remained at that level thereafter. His father died of cardiac failure at age 81 years, whereas his mother had heart failure and died at age 62 years.
At age 75,
Morphologic studies
The biopsy tissues were fixed in 10% buffered formaldehyde and paraffin embedded. Paraffin sections (2 to 4 μm) were stained with hematoxylin and eosin and periodic acid-Schiff (PAS) for light microscopy. Additional tissue was fixed in 2.5% glutaraldehyde in 0.1% Millonig's phosphate buffer. After washing, the tissues were further fixed in 1% osmium tetroxide, dehydrated, and epon embedded. Thin sections were stained on copper palladium grids with uranyl acetate and lead citrate. Stained
Renal morphology
By light microscopy, the biopsy tissues contained cortex and corticomedullary junction with a total of 7 glomeruli, all of which had enlarged podocytes with abundant foamy cytoplasm (Fig 1). The endothelium, mesangium, and glomerular basement membrane were unremarkable. There was focal, mild interstitial fibrosis, and tubular atrophy. Arterioles showed mild to moderate hyalinosis. The biopsy specimen had focal arteriolar smooth muscle vacuoles without eosinophilic inclusions of the classical
Discussion
In 1991, von Scheidt et al17 reported the clinical, morphologic, and biochemical features of the cardiac variant. They described a 54-year-old white male who had isolated myocardial involvement, but none of the classic manifestations of Fabry disease, including angiokeratoma, acroparesthesias, hypohidrosis, corneal and lenticular opacities, or renal insufficiency. An endocardial biopsy showed ultrastructural changes suggestive of Fabry disease, a diagnosis that was confirmed by the
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Cited by (43)
Fabry disease: α-galactosidase A deficiency
2020, Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease: Volume 1An atypical p.N215S variant of Fabry disease with end-stage renal failure
2018, Molecular Genetics and Metabolism ReportsLater Onset Fabry Disease, Cardiac Damage Progress in Silence: Experience With a Highly Prevalent Mutation
2016, Journal of the American College of CardiologyVariations in the GLA gene correlate with globotriaosylceramide and globotriaosylsphingosine analog levels in urine and plasma
2015, Clinica Chimica ActaCitation Excerpt :In the United Kingdom, the GLA p.Asn215Ser mutation was identified in three of the five unrelated men diagnosed with FD on the prospective screening of patients presenting with unexplained LVH at ≥ 40 years of age (n = 79), but in none of those who were diagnosed at < 40 years of age (n = 74) [61]. Males who are hemizygous for this GLA p.Asn215Ser may present with renal dysfunction at advanced age, with the kidney biopsy showing predominant involvement of podocytes and minimal or absence of GSL deposits in other cell types [62], but only exceptionally [63] has the p.Asn215Ser mutation been identified in FD case-finding studies among HD patients. Indeed, the GLA p.Asn215Ser mutation was not detected in any of 13 large-scale studies screening for FD among patients on RRT that were carried out before 2010 (summarized at [64,65]), nor in any of those that have been published subsequently [53,66–70], adding up to more than 20,000 RRT patients screened and more than 30 newly diagnosed carriers of pathogenic GLA mutations.
The attenuated/late onset lysosomal storage disorders: Therapeutic goals and indications for enzyme replacement treatment in Gaucher and Fabry disease
2015, Best Practice and Research: Clinical Endocrinology and Metabolism
Supported in part by grants from the National Institutes of Health, including a Merit Award (5 R37 DK34045), a grant (5 M01 RR00071) for the Mount Sinai General Clinical Research Center, and a grant (5 P30 HD28822) for the Mount Sinai Child Health Research Center.