Lecithin cholesterol acyltransferase deficiency: ultrastructural examination of sequential renal biopsies

We present the renal biopsy findings in two brothers with nephrotic syndrome and lecithin:cholesterol acyltransferase deficiency. Mesangial expansion and capillary wall thickening were accompanied by numerous extracellular osmiophilic membranes within round lucent spaces, by round lamellar deposits, and by amorphous deposits containing thread-like structures with cross-striations. A second biopsy in one of the brothers, when he had developed renal insufficiency 8 yr later, showed increased mesangial and capillary wall thickening. The deposits, which had been in predominantly subepithelial and intramembranous locations, were now in a more prominent subendothelial location. The subepithelial localization of the deposits seen on initial examination may be related to their cationic charge, perhaps with binding to glomerular polyanion, and to uptake by glomerular epithelial cells. The accumulation of lipid is associated with progressive mesangial and glomerular sclerosis.