Early-Onset Lipoprotein Glomerulopathy in a Toddler with Steroid-Resistant Nephrotic Syndrome

Dear Editor,

Steroid-resistant nephrotic syndrome (SRNS) warrants a renal biopsy to delineate the underlying histopathology. We report a toddler with lipoprotein glomerulopathy (LPG), a rare but clinically important cause of SRNS, with a different therapeutic approach.¹

A 2½-year-old male child presented with a short history of progressive generalized edema and nephrotic-range proteinuria. Initial evaluation revealed hypoalbuminemia with preserved renal function, and the child was treated with standard oral prednisolone for presumed nephrotic syndrome. However, failure to achieve remission after 6 weeks prompted a renal biopsy. Histopathological examination demonstrated diffusely enlarged glomeruli with markedly dilated capillary lumina containing laminated lipoprotein thrombi, without immune complex deposition on immunofluorescence, and a positive reaction for Apolipoprotein E immunohistochemistry. Electron microscopy evaluation showed a lamellated appearance of lipid granules in the capillary lumen, and no electron-dense deposits. Together, these findings are diagnostic of LPG [Figure 1].

Close

Figure 1: (a) ApoE immunohistochemistry, 400x. A dilated glomerular capillary shows intense ApoE-positive intraluminal thrombus-like material (arrow). (b) EM, low magnification (scale bar 10 mm), showing a glomerular capillary with lumen distended by finely vacuolated lipoprotein thrombus (arrow). (c) EM, higher magnification (scale bar 1 mm), highlighting the lobulated, lamellated lipoprotein aggregates devoid of electron-dense immune deposits. ApoE:Apolipoprotein E.

Export to PPT

Further evaluation revealed dyslipidemia, and genetic testing confirmed a heterozygous pathogenic mutation in the apolipoprotein E (ApoE) gene (c.127C>T; p.Arg43Cys). Corticosteroids were subsequently tapered and discontinued, and lipid-lowering therapy with atorvastatin was initiated. The child showed rapid clinical and biochemical improvement, with complete resolution of proteinuria and normalization of lipid parameters within 6 weeks.

LPG is a rare autosomal dominant disorder caused by mutations in ApoE, resulting in abnormal lipoprotein metabolism and characteristic intraglomerular lipoprotein thrombi. Fewer than 300 cases have been reported worldwide, with pediatric cases being exceedingly rare and only a handful documented from India. Importantly, immunosuppressive therapies, including corticosteroids, have no proven role in LPG and may unnecessarily expose children to adverse effects.^2,3

Early biopsy and genetic confirmation can prevent unwarranted immunosuppression and allow timely initiation of lipid-targeted therapy. Given the rarity of pediatric LPG and the absence of standardized treatment guidelines, reporting such cases contributes valuable evidence to the existing literature.