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Muscle & Nerve Oct 2004The hepatic porphyrias are a group of rare metabolic disorders characterized by enzymatic defects in the biosynthesis of heme, a metalloporphyrin that is the principal... (Review)
Review
The hepatic porphyrias are a group of rare metabolic disorders characterized by enzymatic defects in the biosynthesis of heme, a metalloporphyrin that is the principal product of porphyrin metabolism. The hepatic porphyrias are genetically transmitted as autosomal-dominant disorders with variable expression that produce a particularly severe form of neuropathy. Most medical students readily recognize acute attacks of porphyria when the classic triad of abdominal pain, psychosis, and neuropathy is present. Yet, porphyric neuropathy is a source of confusion in practice, and patients with porphyria rarely receive the correct diagnosis early in the course of the illness. Porphyric neuropathy is manifest by symptoms, signs, and cerebrospinal fluid abnormalities resembling acute Guillain-Barré syndrome. However, accompanying psychological features, a proximal predilection of asymmetric weakness, and electrodiagnostic findings indicative of an axonal polyradiculopathy or neuronopathy all suggest the diagnosis of porphyria. Confirmation of the diagnosis depends on use of appropriate laboratory studies. The underlying pathophysiology of porphyric neuropathy has not been established, but it may be related to direct neurotoxicity of elevated levels of delta-aminolevulinic acid. The severity of the neuropathy and the availability of potential treatments, including avoidance of provocative factors, make identification important.
Topics: Animals; Electrophysiology; History, 19th Century; History, 20th Century; Humans; Peripheral Nervous System Diseases; Porphyrias, Hepatic; Porphyrins
PubMed: 15372536
DOI: 10.1002/mus.20137 -
Physiological Research 2006In a brief survey the work of Swedish porphyrinologists through time is presented, from the organic chemist Jakob Berzelius 1840 to the molecular biologists of today.... (Review)
Review
In a brief survey the work of Swedish porphyrinologists through time is presented, from the organic chemist Jakob Berzelius 1840 to the molecular biologists of today. The building up in Stockholm of a Swedish national competence centre for porphyria is touched upon and the emergence of a computerized national register on the porphyria gene carriers in the country described. Figures for the prevalences of the seven different forms of porphyria diagnosed in Sweden are given. The geographical distribution of gene mutation spectra is shown for the most frequent form, acute intermittent porphyria. The organisation at Porphyria Centre Sweden of its diagnostic and consultative services is described, as is the decentralized model for porphyria care applied in the form of a clinical network covering the long and sparsely populated country. The ideas and activities of the Swedish Porphyria Patients' Association are presented. Its focus on protection-by-information of the porphyria gene carrier against maltreatment in health service contacts, and against other exposures to environmental threats to his or her health, is discussed. The combined efforts of the national porphyria centre and the patients' association have resulted in early and accurate diagnosis of most of the porphyria gene carriers in the country. The information to the carriers and to the health service regarding the mechanisms of the diseases and the importance of avoiding exposure to disease triggering environmental factors have greatly reduced porphyric morbidity. In the case of the acute porphyrias, by this programme and after the introduction of heme arginate in the therapy, mortality in the acute phase has become extremely rare in Sweden. In contrast, probably due to greater awareness of the high risk for liver cancer in acute porphyrias the number of hepatoma cases diagnosed has increased. The current research activities at the Porphyria Centre which aim at finding ways to substitute the mutated gene in acute intermittent porphyria for an undamaged one, or to substitute the enzyme deficiency by administration of exogenously produced enzyme, are mentioned, as is the work to establish a reliable drug porphyrinogenicity prediction model for evidence based drug counselling.
Topics: Humans; Mutation; Porphyrias; Prevalence; Sweden
PubMed: 17298215
DOI: 10.33549/physiolres.930000.55.S2.109 -
Minerva Anestesiologica May 2002
Review
Topics: Acute Disease; Adult; Anesthesia; Anesthesia, Conduction; Anesthetics; Female; Humans; Porphyrias
PubMed: 12029239
DOI: No ID Found -
Medical Ultrasonography Jun 2024In this series of articles on comments and illustrations of the World Federation for Medicine and Biology (WFUMB) guidelines on contrast-enhanced ultrasound (CEUS), the... (Review)
Review
In this series of articles on comments and illustrations of the World Federation for Medicine and Biology (WFUMB) guidelines on contrast-enhanced ultrasound (CEUS), the topics on very rare focal liver lesions (FLL) are discussed. This article describes the diverse changes of focal liver lesions in peliosis hepatis and the typical changes in porphyria. Although the focus is on the appearance on ultrasound and CEUS, the clinical context is always considered. While peliosis may be a surprising finding on puncture, lesions in porphyria cutanea tarda may be typical visual diagnoses that obviate the need for biopsy. If only you knew. This article aims to sharpen the clinician's eye. It provides knowledge of the clinical presentation and US and CEUS imaging of peliosis hepatis and porphyria.
Topics: Humans; Ultrasonography; Contrast Media; Practice Guidelines as Topic; Peliosis Hepatis; Liver; Porphyrias; Image Enhancement; Diagnosis, Differential
PubMed: 37931015
DOI: 10.11152/mu-4287 -
Journal of Inherited Metabolic Disease Jul 2021
Topics: Acetylgalactosamine; Homocysteine; Humans; Porphyria, Acute Intermittent; Pyrrolidines
PubMed: 34145602
DOI: 10.1002/jimd.12411 -
Hepatology (Baltimore, Md.) Sep 2014Porphyrias are a group of eight metabolic disorders, each resulting from a mutation that affects an enzyme of the heme biosynthetic pathway. Porphyrias are classified as... (Review)
Review
UNLABELLED
Porphyrias are a group of eight metabolic disorders, each resulting from a mutation that affects an enzyme of the heme biosynthetic pathway. Porphyrias are classified as hepatic or erythropoietic, depending upon the site where the gene defect is predominantly expressed. Clinical phenotypes are classified as follows: (1) acute porphyrias with neurovisceral symptoms: acute intermittent porphyria; delta amino-levulinic acid hydratase deficiency porphyria; hereditary coproporphyria; and variegate porphyria and (2) cutaneous porphyrias with skin blistering and photosensitivity: porphyria cutanea tarda; congenital erythropoietic porphyria; hepatoerythropoietic porphyria and both erythropoietic protoporphyrias: autosomal dominant and X-linked. Liver transplantation (LT) may be needed for recurrent and/or life-threatening acute attack in acute intermittent porphyria or acute liver failure or end-stage chronic liver disease in erythropoietic protoporphyria. LT in acute intermittent porphyria is curative. Erythropoietic protoporphyria patients needing LT should be considered for bone marrow transplantation to achieve cure.
CONCLUSION
This article provides an overview of porphyria with diagnostic approaches and management strategies for specific porphyrias and recommendations for LT with indications, pretransplant evaluation, and posttransplant management.
Topics: Humans; Liver Transplantation; Porphyrias
PubMed: 24700519
DOI: 10.1002/hep.27086 -
Annals of Medicine Feb 1994There are seven porphyrias which are caused by defective functions of the enzymes in the haem biosynthesis. Pathogenic mechanisms and symptoms differ greatly in... (Review)
Review
There are seven porphyrias which are caused by defective functions of the enzymes in the haem biosynthesis. Pathogenic mechanisms and symptoms differ greatly in individual porphyrias and, consequently, most of them require a specific therapy. Clinically, the three most important entities are acute porphyric attack, porphyria cutanea tarda and protoporphyria. For an acute porphyric attack the treatment of choice is administration of haem; the other measures are elimination of precipitating factors and symptomatic therapy for many associated symptoms. Porphyria cutanea tarda is controlled by removal of iron by phlebotomies or with low-dose chloroquine. Skin symptoms in protoporphyria can be alleviated with betacaroten but there is no effective procedure to normalize disturbed porphyrin metabolism; hepatic failure seen in some patients may need a liver transplantation. The only effective treatment in congenital erythropoietic porphyria is probably a bone marrow transplantation. No satisfactory treatment is available for very rare delta-aminolevulinic acid dehydrase deficiency porphyria.
Topics: Acute Disease; Humans; Porphyria Cutanea Tarda; Porphyrias
PubMed: 7909442
DOI: 10.3109/07853899409147324 -
The Journal of Investigative Dermatology Mar 1984
Topics: Alcoholism; Bloodletting; Female; Furosemide; Humans; Hydroxychloroquine; Kidney Failure, Chronic; Male; Nalidixic Acid; Porphyrias; Skin Diseases; Terminology as Topic; Tetracycline
PubMed: 6699422
DOI: 10.1111/1523-1747.ep12259984 -
The Israel Medical Association Journal... Apr 2019
Topics: Diagnosis, Differential; Humans; Neglected Diseases; Porphyrias
PubMed: 31032573
DOI: No ID Found -
Current Opinion in Gastroenterology May 2021Acute hepatic porphyrias (AHP) are a group of rare diseases that are characterized by episodic acute neurovisceral pain episodes caused by abnormal accumulation of the... (Review)
Review
PURPOSE OF REVIEW
Acute hepatic porphyrias (AHP) are a group of rare diseases that are characterized by episodic acute neurovisceral pain episodes caused by abnormal accumulation of the neurotoxic porphyrin precursor delta-aminolevulinic acid (ALA). Patient with frequent recurrent acute attacks have been difficult to treat and these patients sometimes require liver transplantation. Recent developments in small interfering RNA (siRNA)-based therapy led to the development of an effective prophylactic treatment for patients with frequent recurrent attacks. This review will describe treatment options for AHP and highlight management in light of new treatment option.
RECENT FINDINGS
Givosiran is a novel siRNA-based therapy targeted specifically to hepatocytes to inhibit ALA synthase 1, the first and rate-limiting step in heme biosynthesis. Patients with frequent recurrent attacks treated with givosiran had durable normalization of ALA and significantly reduced numbers of acute attacks and need for hemin treatment. The overall safety profile for givosiran was comparable with placebo and the drug was recently approved by the Food and Drug Administration for treatment of AHP patients.
SUMMARY
Givosiran is an effective treatment for prevention of acute porphyria attacks in AHP patients with frequent recurrent attacks.
Topics: Humans; Pain; Porphobilinogen Synthase; Porphyria, Acute Intermittent; Porphyrias, Hepatic; Treatment Outcome
PubMed: 33769375
DOI: 10.1097/MOG.0000000000000734