Acute intermittent porphyria in a resource-limited setting: diagnostic pitfalls and emerging therapeutic perspectives

Acute intermittent porphyria (AIP) is a rare metabolic disorder caused by deficiency of hydroxymethylbilane synthase (HMBS), leading to accumulation of neurotoxic heme precursors. Its protean neurovisceral manifestations and the possibility of false-negative biochemical assays make diagnosis challenging, particularly in low- and middle-income countries (LMICs), where access to specialized diagnostics and definitive therapy is often limited. We report a 32-year-old woman with recurrent episodes of abdominal pain, vomiting, hyponatremia, episodic hypertension, and neurological deficits who underwent extensive evaluation at multiple centers without a unifying diagnosis. Despite repeated negative qualitative urinary porphobilinogen (PBG) assays, strong clinical suspicion was maintained, supported by bedside observation of progressive urine darkening on light exposure. Repeat testing during an acute symptomatic phase confirmed elevated urinary PBG and δ-aminolevulinic acid (ALA) levels, and genetic analysis identified a pathogenic HMBS mutation (c.77G>A; p.Arg26His), establishing the diagnosis of AIP. The patient was managed with high-carbohydrate supplementation and supportive care, as intravenous hemin was unavailable. This case illustrates common diagnostic pitfalls in AIP, including overreliance on negative qualitative screening tests, fragmented symptom-based management, and limited access to quantitative assays in resource-constrained settings. Recent advances, including standardized biochemical testing, confirmatory genetic analysis, and disease-modifying therapy with givosiran, have transformed AIP management in high-income countries; however, their limited availability in LMICs continues to result in diagnostic delay and therapeutic inequity.