Congenital nephrotic syndrome in a newborn with glycogen storage disease and Wilms tumor 1 (WT1) mutation

Genetic disorders in neonates often present with overlapping clinical features, posing significant diagnostic challenges. Glycogen storage diseases (GSD) disrupt glycogen metabolism, leading to energy deficits. Pathogenic variants in the Wilms tumor 1 (WT1) gene represent a rare but significant cause of early-onset steroid-resistant nephrotic syndrome (SRNS), associated with a broad range of both kidney and extrakidney phenotypic manifestations. The coexistence of these genetic diseases in a single patient has not been previously reported. Herein, we present a case of a newborn with symptomatic hypoglycemia and metabolic acidosis that was transferred to the Neonatal Intensive Care Unit. During hospitalization, he developed hyponatremia and nephrotic-range proteinuria, a genetic test was performed, and he was transferred to the nephrology unit. Genetic analysis identified a compound homozygous mutation (c.247 C > T) in the G6PC gene, confirming glycogen storage disease type 1a (GSD-1a) and a pathogenic WT1 mutation (c.1400G > A) associated with Denys-Drash syndrome. This case highlights the importance of a multidisciplinary approach in the evaluation and management of neonates with a complex combination of genetically-determined conditions.