Biochemically Evolving Acute Hepatic Porphyria With Postpartum Progression to Severe Recurrent Neurovisceral Disease.

Acute hepatic porphyria (AHP) is a group of rare metabolic disorders of hepatic heme biosynthesis characterized by episodic neurovisceral crises resulting from the accumulation of neurotoxic heme precursors, particularly δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). Despite the availability of biochemical testing, diagnosis is frequently delayed because of fluctuating disease expression, non-specific clinical manifestations, normal structural imaging, and challenges related to the timing of biochemical sampling. We report the case of a 34-year-old female patient with a prolonged six-year history of recurrent unexplained neurovisceral attacks involving severe abdominal pain, nausea, vomiting, anorexia, autonomic instability, weakness, fatigue, dark urine, and progressive neuropathic manifestations. She underwent extensive evaluations across multiple healthcare systems in the United Arab Emirates, India, and Thailand without a unifying diagnosis. AHP was clinically suspected approximately two years before biochemical confirmation because of the highly stereotyped phenotype and reproducible response to 10% dextrose and intravenous hemin despite initially negative ALA and PBG studies. The disease entered complete remission during pregnancy, followed by dramatic postpartum escalation with recurrent hospitalizations, hemin dependence, progressive neurological involvement, autonomic dysfunction, and weight loss. Serial porphyrin fractionation demonstrated persistent and progressive elevation of uroporphyrins and coproporphyrin III before eventual capture of elevated urinary ALA and PBG through strict pre-treatment sampling. Extensive evaluation excluded mitochondrial disease, heavy metal toxicity, Wilson's disease, organic acidemias, fatty-acid oxidation defects, inflammatory abdominal disease, and structural pathology. Whole-genome sequencing was negative for pathogenic AHP variants, highlighting the limitations of genetics when the clinicobiochemical phenotype is compelling. The patient was transitioned to givosiran after developing recurrent hemin-dependent attacks with progressive neurological and autonomic involvement. This case highlights the evolving biochemical nature of AHP, the diagnostic pitfalls, the limitations of isolated laboratory interpretation, the importance of correct sampling timing, the diagnostic significance of mechanism-directed therapeutic response, the critical role of longitudinal phenotype-driven clinical reasoning in rare metabolic disease, and the transformative role of targeted therapy.