Uncontrolled Acute Intermittent Porphyria as a Cause of Spontaneous Abortion

Abstract

Introduction:The association of acute intermitetn porphyria (AIP) with pregnancy and as a cause of spontaneous abortion is rare. Aim: To show a case of AIP known before pregnancy in a patient who had a spontaneous abortion. Case report: A gynecologist examined 26-yearold patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Her therapy was dydrogesterone. In consultation with an anesthesiologist, a short intravenous anesthesia, vacuum aspiration, and curettage were performed.During hospitalization, the patient ceased to take harmful drugs and she was given haemarginate, glucose and symptomatic drugs, and she recovered completely. Conclusion: Treatment of threatened spontaneous abortion in AIP remains the subject of dilemma and controversy, and future research is needed.

Assessment of porphyrogenicity of drugs and chemicals in selected hepatic cell culture models through a fluorescence‐based screening assay

“…β‐estradiol and norgestrel were used to represent the estrogen and progestogen classes, respectively, and we found that, at higher concentrations, both led to a notable accumulation of PP, especially in the presence of DFO (Figure 2). Norgestrel, however, produced greater fluorescence readings than β‐estradiol, which is in keeping with clinical impressions and observations in human subjects 2,47–52 . We also tested alpha‐methyldopa because it continues often to be used to control systemic arterial hypertension in pregnant women.…”

“…Norgestrel, however, produced greater fluorescence readings than β‐estradiol, which is in keeping with clinical impressions and observations in human subjects. 2 , 47 , 48 , 49 , 50 , 51 , 52 We also tested alpha‐methyldopa because it continues often to be used to control systemic arterial hypertension in pregnant women. Although the drug had a low CC 50 of 0.164 mM in the presence of DFO, it did not lead to an appreciable accumulation of PP below concentrations that led to appreciable cytotoxicity.…”

“…Norgestrel, however, produced greater fluorescence readings than β-estradiol, which is in keeping with clinical impressions and observations in human subjects. 2,[47][48][49][50][51][52] We also tested alpha-methyldopa because it continues often to be used to control systemic arterial hypertension in pregnant women.…”

Recurrent symptoms of acute intermittent porphyria after biochemical normalization with givosiran—An ongoing clinical conundrum

“…This patient reported more frequent porphyric attacks during her menstrual cycles, specifically around ovulation, which is a common finding among women with AIP. Estrogen and progesterone induce ALAS‐1, increasing the levels of porphyrin intermediates, which play a role in causing acute attacks 9,10 . This is further supported by results of a recent study that used an in vitro drug fluorescence screening assay to test for porphyrogenicity; both β‐estradiol and norgestrel, drugs in the estrogen and progestogen classes, respectively, led to a significant accumulation of protoporphyrins 11 .…”

“…Estrogen and progesterone induce ALAS-1, increasing the levels of porphyrin intermediates, which play a role in causing acute attacks. 9,10 This is further supported by results of a recent study that used an in vitro drug fluorescence screening assay to test for porphyrogenicity; both β-estradiol and norgestrel, drugs in the estrogen and progestogen classes, respectively, led to a significant accumulation of protoporphyrins. 11 Our patient continued to have low ALA and PBG even during her menstrual cycles, so it is still unclear what the etiology and pathogenesis are for her ongoing symptoms.…”