Dysregulation of homocysteine homeostasis in acute intermittent porphyria patients receiving heme arginate or givosiran

2021 ◽  
Author(s):  
Jordi To‐Figueras ◽  
Robin Wijngaard ◽  
Judit García‐Villoria ◽  
Aasne K. Aarsand ◽  
Paula Aguilera ◽  
...  
Keyword(s):  
Acute Intermittent Porphyria ◽  
Heme Arginate

scholarly journals Prophylactic Heme Arginate Infusion for Acute Intermittent Porphyria

2021 ◽  
Vol 12 ◽  
Author(s):  
Hung-Chou Kuo ◽  
Chia-Ni Lin ◽  
Yi-Fen Tang
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Acute Intermittent Porphyria ◽  
Porphobilinogen Deaminase ◽  
Attack Frequency ◽  
Weekly Administration ◽  
Clinical Counseling ◽  
Heme Arginate ◽  
Before And After

Objectives: This study aimed to evaluate the efficacy of long-term weekly prophylactic heme arginate (HA) infusions in reducing attack frequency and severity in female AIP patients.Methods: We report the results of five female AIP patients with frequent recurrent attacks (>9/year) before and after institution of weekly prophylaxis with heme arginate (3 mg/kg body weight). All five cases had confirmed disease-associated mutations in the porphobilinogen deaminase gene, and all had received genetic and clinical counseling about AIP.Results: In the five included patients, average annual attack rate (AAR) in the year prior to HA prophylaxis was 11.82 (range 9.03–17.06), and average total HA usage was 32.60 doses (range: 13.71–53.13). After 2.58–14.64 years of HA prophylaxis, average AAR was reduced to 2.23 (range 0.00–5.58), and attack severity (i.e., doses required per attack) was reduced from 2.81 to 1.39 doses/attack. Liver and renal function remained stable during weekly administration of HA prophylaxis. The most common complications were port-A catheter-related events. No other complications or safety concerns occurred with long-term use of HA prophylaxis.Conclusion: Our study demonstrated women with AIP receiving weekly prophylactic HA infusions resulted in fewer episodes that required acute HA treatment while maintaining stable renal and liver function. Weekly prophylactic HA infusions effectively prevent frequent porphyric attacks and reduce attack severity.

Ferriporphyrins and endothelium: a 2-edged sword—promotion of oxidation and induction of cytoprotectants

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3442-3450 ◽  
Author(s):  
József Balla ◽  
György Balla ◽  
Viktoria Jeney ◽  
György Kakuk ◽  
Harry S. Jacob ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Free Radical ◽  
Heme Oxygenase ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acute Intermittent Porphyria ◽  
Fold Increase ◽  
Heme Arginate ◽  
Activated Neutrophils ◽  
Fold Induction

Heme arginate infusions blunt the symptoms of patients with acute intermittent porphyria without evidence of the vascular or thrombotic side effects reported for hematin. To provide a rationale for heme arginate's safety, the present study examined the effects of various ferriporphyrins to sensitize human endothelial cells to free radical injury and to induce heme oxygenase and ferritin expression. Heme arginate, unlike hematin, did not amplify oxidant-induced cytotoxicity mediated by hydrogen peroxide (5.3 ± 2.4 versus 62.3 ± 5.3% 51Cr release,P < .0001) or by activated neutrophils (14.4 ± 2.9 versus 41.1 ± 6.0%, P < .0001). Nevertheless, heme arginate efficiently entered endothelial cells similarly to hematin, since both markedly induced heme oxygenase mRNA (more than 20-fold increase) and enzyme activity. Even with efficient permeation, endothelial cell ferritin content was only minimally increased by heme arginate compared with a 10-fold induction by hematin; presumably less free iron was derived from heme arginate despite up-regulation of heme oxygenase. Hematin is potentially vasculopathic by its marked catalysis of oxidation of low-density lipoprotein (LDL) to endothelial-toxic moieties. Heme arginate was significantly less catalytic. Heme arginate–conditioned LDL was less than half as cytotoxic to endothelial cells as hematin-conditioned LDL (P < .004). It is concluded that heme arginate may be less vasculotoxic than hematin since it is an effective heme oxygenase gene regulator but a less efficient free-radical catalyst.

scholarly journals Liver Transplantation because of Acute Liver Failure due to Heme Arginate Overdose in a Patient with Acute Intermittent Porphyria

2012 ◽  
Vol 6 (1) ◽  
pp. 190-196 ◽  
Author(s):  
Pascal Frei ◽  
Elisabeth I. Minder ◽  
Natascia Corti ◽  
Beat Muellhaupt ◽  
Andreas Geier ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Acute Intermittent Porphyria ◽  
Heme Arginate

scholarly journals Liver Fibrosis Associated with Iron Accumulation Due to Long-Term Heme-Arginate Treatment in Acute Intermittent Porphyria: A Case Series

2015 ◽  
pp. 77-81 ◽  
Author(s):  
Barbara Willandt ◽  
Janneke G. Langendonk ◽  
Katharina Biermann ◽  
Wouter Meersseman ◽  
François D’Heygere ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Case Series ◽  
Acute Intermittent Porphyria ◽  
Iron Accumulation ◽  
Heme Arginate

Ferriporphyrins and endothelium: a 2-edged sword—promotion of oxidation and induction of cytoprotectants

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3442-3450 ◽  
Author(s):  
József Balla ◽  
György Balla ◽  
Viktoria Jeney ◽  
György Kakuk ◽  
Harry S. Jacob ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Free Radical ◽  
Heme Oxygenase ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acute Intermittent Porphyria ◽  
Fold Increase ◽  
Heme Arginate ◽  
Activated Neutrophils ◽  
Fold Induction

Abstract Heme arginate infusions blunt the symptoms of patients with acute intermittent porphyria without evidence of the vascular or thrombotic side effects reported for hematin. To provide a rationale for heme arginate's safety, the present study examined the effects of various ferriporphyrins to sensitize human endothelial cells to free radical injury and to induce heme oxygenase and ferritin expression. Heme arginate, unlike hematin, did not amplify oxidant-induced cytotoxicity mediated by hydrogen peroxide (5.3 ± 2.4 versus 62.3 ± 5.3% 51Cr release,P &lt; .0001) or by activated neutrophils (14.4 ± 2.9 versus 41.1 ± 6.0%, P &lt; .0001). Nevertheless, heme arginate efficiently entered endothelial cells similarly to hematin, since both markedly induced heme oxygenase mRNA (more than 20-fold increase) and enzyme activity. Even with efficient permeation, endothelial cell ferritin content was only minimally increased by heme arginate compared with a 10-fold induction by hematin; presumably less free iron was derived from heme arginate despite up-regulation of heme oxygenase. Hematin is potentially vasculopathic by its marked catalysis of oxidation of low-density lipoprotein (LDL) to endothelial-toxic moieties. Heme arginate was significantly less catalytic. Heme arginate–conditioned LDL was less than half as cytotoxic to endothelial cells as hematin-conditioned LDL (P &lt; .004). It is concluded that heme arginate may be less vasculotoxic than hematin since it is an effective heme oxygenase gene regulator but a less efficient free-radical catalyst.

scholarly journals Prophylactic heme arginate therapy in acute intermittent hepatic porphyria - a case report

2021 ◽  
pp. 9-9
Author(s):  
Zarko Krnetic ◽  
Tatjana Pesic ◽  
Zeljka Savic ◽  
Tatiana Jocic ◽  
Olgica Latinovic-Bosnjak ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Case Report ◽  
Acute Intermittent Porphyria ◽  
Therapeutic Modality ◽  
Beneficial Effects ◽  
Heme Arginate ◽  
Predominantly Female ◽  
Hospital Days ◽  
Gonadorelin Analogue

Introduction. Among the acute hepatic porphyrias, a small percentage of patients, predominantly female, present with recurrent cyclic attacks of acute intermittent porphyria (AIP) that occurs more than three times a year, and sometimes at intervals of less than a month. In women, the attacks are typically related to menstrual cycle, requiring several days of hospitalization and administration of heme arginate. For these patients, the prophylactic heme arginate therapy may be the optimal treatment modality. Case Report. We present a 40-year-old female patient who has been suffering from porphyria for seventeen years. The first attack occurred in 2003, presenting with severe neurological symptoms, requiring the use of heme arginate Normosang?, which resulted in a favorable therapeutic response. In 2004 and 2007, gonadorelin analogue Zoladex? (goserelin) was used, but without beneficial effects on the course of the disease. In 2008, a preventive administration of heme arginate was initiated. The patient received heme arginate in the early phase of symptoms, every month in the premenstrual phase of the cycle, which resulted in milder symptoms, full recovery within 24 hours, lower doses of Normosang? (1-2 ampoules) and fewer hospital days (1-2 days) per month. This regimen has significantly improved the patient's quality of life and reduced the risk of potential adverse effects. Conclusion. Preventive use of Normosang? is the optimal therapeutic modality in patients with frequent, recurrent severe attacks that are unresponsive to other therapeutic regimens. As a result, patients have a better quality of life due to an effective, short-term, targeted treatment regimen.

Anesthetic management for a patient with acute intermittent porphyria treated with heme arginate

1999 ◽  
Vol 13 (2) ◽  
pp. 115-118 ◽  
Author(s):  
Seiji Takaoka ◽  
Hisao Tanaka ◽  
Sumio Amagasa ◽  
Mayumi Yamakawa ◽  
Ritsuko Fukuda ◽  
...  
Keyword(s):  
Anesthetic Management ◽  
Acute Intermittent Porphyria ◽  
Heme Arginate

scholarly journals A Young Lady with Recurrent Acute Abdomen

2020 ◽  
Vol 5 (5) ◽  
Keyword(s):  
Acute Abdomen ◽  
Hospital Admissions ◽  
Gastrointestinal Symptoms ◽  
Specific Treatment ◽  
Acute Intermittent Porphyria ◽  
Acute Attack ◽  
Medical Disorders ◽  
High Clinical Suspicion ◽  
Heme Arginate ◽  
Married Female

Acute intermittent porphyria (AIP) is a rare autosomal dominant hereditary metabolic disorder having protean manifestations. It usually presents with short duration of gastrointestinal symptoms followed by rapidly progressive fulminant neurological syndrome. It is a neurological emergency and mimics many other psychiatric and medical disorders and can be fatal if it remains undiagnosed and untreated. Further, specific treatment in the form of Heme arginate is not universally available and very costly, so high clinical suspicion and early diagnosis and management of acute attack and prevention of further attacks are very important. Here, we report a 23 years old married female nurse presenting with recurrent acute abdomen requiring frequent hospital admissions along with convulsion during her last attack. The presence of porphyrins in urine confirms the diagnosis of AIP.

scholarly journals A Case of Recurrent Acute Abdomen in a Young Lady Masquerading as Somatoform Disorder

2021 ◽  
Vol 6 (2) ◽  
pp. 01-03
Author(s):  
Richmond Gomes
Keyword(s):  
Acute Abdomen ◽  
Hospital Admissions ◽  
Gastrointestinal Symptoms ◽  
Specific Treatment ◽  
Acute Intermittent Porphyria ◽  
Acute Attack ◽  
Somatoform Disorder ◽  
Medical Disorders ◽  
High Clinical Suspicion ◽  
Heme Arginate

Acute intermittent porphyria (AIP) is a rare autosomal dominant hereditary metabolic disorder having protean manifestations. It usually presents with short duration of gastrointestinal symptoms followed by rapidly progressive fulminant neurological syndrome. It is a neurological emergency and mimics many other psychiatric and medical disorders and can be fatal if it remains undiagnosed and untreated. Further, specific treatment in the form of Heme arginate is not universally available and very costly, so high clinical suspicion and early diagnosis and management of acute attack and prevention of further attacks are very important. Here, we report a 23 years old married female nurse presenting with recurrent acute abdomen requiring frequent hospital admissions along with convulsion during her last attack. The presence of porphyrins in urine confirms the diagnosis of AIP.

scholarly journals A Commonly Missed Well Known Entity- Acute Intermittent Porphyria: A Case Report

2020 ◽  
Vol 1 (6) ◽  
pp. 01-03
Author(s):  
Richmond Ronald Gomes
Keyword(s):  
Hospital Admissions ◽  
Gastrointestinal Symptoms ◽  
Specific Treatment ◽  
Acute Intermittent Porphyria ◽  
Acute Attack ◽  
Medical Disorders ◽  
High Clinical Suspicion ◽  
Heme Arginate ◽  
Female Nurse ◽  
Married Female

Acute intermittent porphyria (AIP) is a rare autosomal dominant hereditary metabolic disorder having protean manifestations. It usually presents with short duration of gastrointestinal symptoms followed by rapidly progressive fulminant neurological syndrome. It is a neurological emergency and mimics many other psychiatric and medical disorders and can be fatal if it remains undiagnosed and untreated. Further, specific treatment in the form of Heme arginate is not universally available and very costly, so high clinical suspicion and early diagnosis and management of acute attack and prevention of further attacks are very important. Here, we report a 23 years old married female nurse presenting with recurrent acute abdomen requiring frequent hospital admissions along with convulsion during her last attack. The presence of porphyrins in urine confirms the diagnosis of AIP.

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