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. 730₇31del; 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.
Phyo et al. (Wed,) studied this question.