SIADH as an Underrecognized Manifestation of Porphyria-like Crises in Hereditary Tyrosinemia Type 1: Clinical and Pathophysiological Insights.

Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disorder caused by fumarylacetoacetate hydrolase deficiency, leading to the accumulation of toxic metabolites such as fumarylacetoacetate (FAA) and succinylacetone (SA). We report an 11-year-old boy with poorly controlled HT1 who presented with a severe neurovisceral crisis after suboptimal adherence to nitisinone (NTBC) therapy, characterized by abdominal pain, hypertension, paralytic ileus, seizures, and profound hyponatremia. Biochemical evaluation revealed markedly elevated urinary δ-aminolevulinic acid (ALA), consistent with a porphyria-like metabolic decompensation, together with inappropriately increased plasma copeptin in the setting of hypotonic hyponatremia and clinical euvolemia, fulfilling diagnostic criteria for the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Optimization of NTBC therapy combined with tailored fluid management resulted in complete clinical and biochemical recovery. This case supports a pathophysiological link between acute disruption of the heme-porphyrin pathway and inappropriate antidiuretic hormone secretion. In HT1, this susceptibility may be further amplified by FAA- and SA-mediated oxidative stress, mitochondrial dysfunction, and heme depletion, with an additional contribution from SA-associated renal tubular impairment. Overall, our findings underscore SIADH as a potentially underrecognized cause of acute hyponatremia in HT1 and highlight the importance of strict NTBC adherence and early monitoring of urinary ALA during metabolic decompensation.