2026-07-01 | Advanced Management of Acute Intermittent Porphyria: The Role of Givosiran Therapy in Improving Long‐Term Outcomes‐A Case Study
ABSTRACT Acute intermittent porphyria is a rare disorder causing neurotoxic precursor accumulation and severe neurological complications. We report a case progressing to tetraplegia and respiratory failure with delayed diagnosis. Treatment with hemin and givosiran resulted in prevention of attacks and functional recovery, highlighting the importance of early diagnosis and long‐term therapy.
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2026-07-01 | Diagnosis and management of acute intermittent porphyria in teenage fraternal twins
Background Acute intermittent porphyria (AIP) is a rare autosomal dominant disorder caused by pathogenic variants in hydroxymethylbilane synthase ( HMBS ). Different factors including hormonal fluctuations trigger neurovisceral attacks. Pediatric data on prophylactic therapies, particularly the small interfering RNA therapeutic givosiran, remain limited. Case presentation We report dizygotic/fraternal twin teenage girls, both 15 years old, who presented separately with acute abdominal and hip pain, hypertension, and tachycardia. In both patients, symptoms were temporally associated with menses and reduced oral intake. Biochemical evaluation revealed markedly elevated urinary δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). Genetic testing confirmed a heterozygous pathogenic HMBS variant (c.730_731del; p.Leu244Alafs⁎6) in both patients. Acute attacks were treated with intravenous hemin (4 mg/kg/day for four days with significant symptom resolution). Recurrent attacks in Patient A initially prompted prophylactic monthly hemin infusion, followed by transition to subcutaneous givosiran (2.5 mg/kg monthly). Patient B had a milder clinical course but was also started on prophylactic therapy after shared decision-making because of her confirmed genotype, biochemical activity, strong family history, and her fraternal twin sister’s recurrent course. Both patients demonstrated sustained reductions in urinary PBG and absence of recurrent attacks on givosiran. Despite sharing the same familial pathogenic HMBS variant, the twins exhibited variable disease severity, with Patient B ultimately requesting a supervised trial discontinuation of givosiran after a prolonged attack-free period. Conclusion This case series highlights the diagnostic approach to AIP in adolescents and adds to the limited pediatric experience with givosiran. Phenotypic variability despite identical HMBS variants underscores incomplete penetrance, potential genetic or epigenetic modifiers, environmental triggers, and the need for individualized management.
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2026-06-29 | 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.
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