OBSOLETE: Familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis

Familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis is an obsolete Orphanet classification (ORPHA:93217) that was previously used to describe a hereditary form of nephrotic syndrome characterized by resistance to corticosteroid therapy and a specific kidney biopsy pattern known as diffuse mesangial sclerosis (DMS). This condition primarily affects the kidneys, where the glomeruli — the tiny filtering units — undergo progressive scarring (sclerosis) of the mesangial region, leading to massive protein loss in the urine (proteinuria), low blood protein levels (hypoalbuminemia), generalized swelling (edema), and elevated blood lipids (hyperlipidemia). Onset is typically in infancy or early childhood, and the disease often progresses rapidly to end-stage kidney disease. This entity has been reclassified and is now subsumed under broader categories of genetic steroid-resistant nephrotic syndrome (SRNS). Mutations in several genes have been identified as causes of familial SRNS with DMS, including NPHS1 (nephrin), NPHS2 (podocin), WT1, PLCE1 (phospholipase C epsilon 1), and LAMB2 (laminin beta-2), among others. The inheritance pattern varies depending on the specific genetic cause but is most commonly autosomal recessive. Because the condition does not respond to standard immunosuppressive therapies including corticosteroids and calcineurin inhibitors, management is largely supportive, focusing on controlling edema with diuretics, managing complications of nephrotic syndrome, and ultimately kidney transplantation when end-stage renal disease develops. Genetic testing is important for confirming the diagnosis, guiding treatment decisions, and providing accurate genetic counseling to affected families.

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