Fanconi Syndrome (FS) is a proximal renal tubular dysfunction characterised by the urinary loss of normally reabsorbed substances. Although rare, it may occur as an iatrogenic complication of valproic acid (VPA) therapy in children. The paper reports the case of a 3-year-old boy (Trisomy 21, PEG-fed) treated with VPA for six months. The patient presented with dependent oedema and weight gain. Laboratory tests revealed significant proteinuria (PrU/CrU 5.9 mg/mg), glycosuria, alkaline urinary pH and reduced tubular reabsorption of phosphorus (TRP 64%). Blood tests confirmed metabolic acidosis, hypophosphataemia and hypouricaemia with preserved renal function. The clinical picture is consistent with VPA-induced acquired FS. The pathogenesis is linked to mitochondrial toxicity in the proximal tubule, driven by the inhibition of β-oxidation and depletion of carnitine and coenzyme A. Management involved the gradual discontinuation of VPA and enteral electrolyte supplementation and led to progressive metabolic recovery. This case highlights the necessity of monitoring tubular function in paediatric patients on long-term valproate therapy.