2026-07-12 | Tolerability of hormonal treatments in acute hepatic porphyria patients.
Acute hepatic porphyria (AHP) flares have been associated with female hormones and the use of hormonal treatments. Women with AHP are traditionally advised to avoid exogenous oestrogen and progesterone, limiting options for contraception and management of menorrhagia, dysmenorrhoea and menopausal symptoms. Evidence on specific hormonal therapies is limited; a 2003 study found that 25% of women with acute intermittent porphyria (AIP) experienced attacks with contraceptives containing progesterone, oestrogen or both. To update the current understanding of the tolerability of hormonal treatments in women with AHP. An anonymous questionnaire was distributed to women with AHP (acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) via hospital records and a national patient support group, capturing prior hormonal therapy use and associated flares. Thirty responses were analysed; 23 participants had used hormonal therapies. Flares were most frequent in hereditary coproporphyria (66%) and less common in variegate porphyria and acute intermittent porphyria (~20%). No flares were reported with hormone replacement therapy, the progesterone-only pill or progesterone implants. Flares occurred with combined oral contraceptives (46.6%) and progesterone-containing intrauterine devices (28.5%), particularly drospirenone-containing pills. Levonorgestrel-based therapies, including the Mirena IUD, were better tolerated and often improved symptoms. Although limited by sample size and retrospective design, this study provides clinically useful data on the tolerability of specific hormonal therapies in women with AHP, supporting personalised prescribing and patient counselling for contraception and symptom management.
Open article ↗
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.
Open article ↗
2026-06-19 | [Acute intermittent porphyria: When diagnostic errance jeopardizes patient health].
Acute intermittent porphyria is a rare genetic disorder characterized by an enzyme deficiency in heme synthesis, causing an accumulation of neurotoxic precursors. Its clinical symptoms include abdominal and/or lumbar pain, reddish-brown urine, and neuropsychiatric signs. We report the case of a young female patient who presented with several episodes of intense low back pain followed by confusion, visual hallucinations, epileptic seizures, and severe dysautonomia with hypotension and impaired alertness. The diagnosis was established after several weeks of investigation, one year after the onset of symptoms. The course of the disease was marked by an early relapse without any triggering factor, which led to treatment with givosiran, which was spectacularly successful. Treatment-induced hyperhomocysteinemia was successfully corrected with pyridoxine. It is essential to be aware of the epidemiology, risk factors, and suggestive symptoms of this potentially serious treatable disease to reduce diagnostic uncertainty, limit long-term complications, and improve prognosis.
Open article ↗
