Contributed by Amber Henry, MD and Sheldon Bastacky, MD
CLINICAL HISTORY AND CASE PRESENTATION:
FD is a 36-year-old white woman with a history of an inherited genetic disease, diagnosed in 1999 when she was found to have a low leukocyte alpha-galactosidase enzyme level. She also has a remote history of headaches, tinnitus, vertigo, acroparesthesias, and angiokeratomas. There is extensive family involvement with this particular genetic disease, and those affected include her father, her teenage son, and two sisters. Her father died at age 49 from complications of cardiovascular and renal disease. The patient has no reported history of diabetes or hypertension; her recent blood pressure is 112/74 mmHg. An echocardiogram showed a normal left ventricular size and an ejection fraction of 60%. Pertinent laboratory values include: BUN 13 mg/dL, creatinine 0.6 mg/dL, hemoglobin 13.2 gm/dL, hematocrit 36.6%, and glucose 81 mg/dL. Urine analysis shows trace protein with no cells. The patient has no peripheral edema. She had microalbuminuria with urine albumin 4.2 mg/dL.
Persistent microalbuminuria, in the absence of diabetes, hypertension, and other possible causes of microalbuminuria, prompted evaluation with a percutaneous renal core biopsy. The tissue examined by light microscopy consists of renal cortex and medulla (Figure 1). The profiles of approximately 26 glomeruli are identified in the paraffin, frozen, and plastic sections, of which one glomerulus located near the capsule is globally sclerotic (Figures 2 and 3). The non-obsolescent glomeruli are normocellular. The majority of the glomeruli show diffuse vacuolated foamy cell change in the podocyte cytoplasm (Figures 4, 5, 6 and 7). The tubules show rare atrophy, hyaline casts, and red blood cells. Methenamine silver-trichrome stain reveals the presence of protein resorption droplets in several proximal tubular epithelial cells. There is a mild patchy chronic lymphocytic inflammation present in the interstitium. Approximately eight small arteries and six arterioles are identified in the paraffin, frozen, and plastic sections. One of the small arteries shows mild to moderate mural wall thickening (Figure 8). There is no evidence of vasculitis, thromboemboli, or thrombotic microangiopathy.
The toluidine blue stained plastic sections demonstrate prominent zebra bodies (myeloid inclusions) in the podocytes (Figure 9). Electron microscopy clearly shows these inclusions are present ultrastructurally within parietal epithelial cells and podocytes (Figures 10, 11, and 12). There is extensive podocyte foot process effacement and the glomerular basement membrane is mildly thickened in some areas (up to 500 nanometers, normal 250-400 nanometers) (Figure 13). The mesangial areas are unremarkable. The endothelial cells are unremarkable, without cytoplasmic tubuloreticular inclusions. Rare tubular epithelial cells contain protein resorption droplets (Figure 14). Several arterioles contain myeloid inclusions within a few of the smooth muscle cells within the wall (Figure 15). There is no evidence of an immune complex deposition disorder.
Immunofluorescence microscopy demonstrates rare hyaline casts and protein resorption droplets. There is non-specific granular mesangial staining with IgM predominance (Figure 16).