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      Acute Intermittent Porphyria: Current Perspectives And Case Presentation

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          Abstract

          Acute intermittent porphyria (AIP) is an autosomal dominant metabolic disorder characterized by a deficiency in heme biosynthesis. Heme biosynthesis occurs throughout the body, but it is most prominent in the erythroblastic system and liver. AIP is a hepatic porphyria whereby the liver is the source of toxic heme metabolites. Clinical manifestations of AIP result from a genetic mutation that leads to partial function of porphobiliogen deaminase (PBGD). This causes an accumulation of upstream, neurotoxic metabolites. Symptoms include but are not limited to peripheral neuropathies, autonomic neuropathies and psychiatric manifestations. AIP can be life threatening and clinical signs and symptoms are often heterogeneous and non-specific. Therefore, it is important to be able to recognize these patients to make a prudent diagnosis and offer appropriate therapy. Here, we review the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of AIP including the role of liver transplantation.

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          Porphyrias.

          Hereditary porphyrias are a group of eight metabolic disorders of the haem biosynthesis pathway that are characterised by acute neurovisceral symptoms, skin lesions, or both. Every porphyria is caused by abnormal function of a separate enzymatic step, resulting in a specific accumulation of haem precursors. Seven porphyrias are the result of a partial enzyme deficiency, and a gain of function mechanism has been characterised in a new porphyria. Acute porphyrias present with acute attacks, typically consisting of severe abdominal pain, nausea, constipation, confusion, and seizure, and can be life-threatening. Cutaneous porphyrias present with either acute painful photosensitivity or skin fragility and blisters. Rare recessive porphyrias usually manifest in early childhood with either severe cutaneous photosensitivity and chronic haemolysis or chronic neurological symptoms with or without photosensitivity. Porphyrias are still underdiagnosed, but when they are suspected, and dependent on clinical presentation, simple first-line tests can be used to establish the diagnosis in all symptomatic patients. Diagnosis is essential to enable specific treatments to be started as soon as possible. Screening of families to identify presymptomatic carriers is crucial to decrease risk of overt disease of acute porphyrias through counselling about avoidance of potential precipitants. Copyright 2010 Elsevier Ltd. All rights reserved.
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            An update of clinical management of acute intermittent porphyria

            Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP patients for long-term complications: chronic hypertension, chronic kidney insufficiency, chronic pain syndrome, and hepatocellular carcinoma.
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              Update review of the acute porphyrias.

              Acute porphyrias are rare inherited disorders due to deficiencies of haem synthesis enzymes. To date, all UK cases have been one of the three autosomal dominant forms, although penetrance is low and most gene carriers remain asymptomatic. Clinical presentation is typically with acute neurovisceral attacks characterised by severe abdominal pain, vomiting, tachycardia and hypertension. Severe attacks may be complicated by hyponatraemia, peripheral neuropathy sometimes causing paralysis, seizures and psychiatric features. Attacks are triggered by prescribed drugs, alcohol, hormonal changes, fasting or stress. The diagnosis is made by finding increased porphobilinogen excretion in a light-protected random urine sample. Management includes administration of intravenous human haemin and supportive treatment with non-porphyrinogenic drugs. A few patients develop recurrent attacks, a chronic illness requiring specialist management. Late complications include chronic pain, hepatocellular carcinoma, chronic renal failure and hypertension. In the UK, the National Acute Porphyria Service provides clinical advice and supplies haemin when indicated.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                TCRM
                tcriskman
                Therapeutics and Clinical Risk Management
                Dove
                1176-6336
                1178-203X
                16 December 2019
                2019
                : 15
                : 1443-1451
                Affiliations
                [1 ]Department of Medicine, Division of Gastroenterology, Duke University School of Medicine , Durham, NC, USA
                [2 ]Department of Medicine, Division of Gastroenterology, Vanderbilt University Medical Center , Nashville, TN, USA
                [3 ]Department of Medicine, Duke University School of Medicine , Durham, NC, USA
                [4 ]Department of Medicine, Duke Clinical Research Institute , Durham, NC, USA
                Author notes
                Correspondence: Julius Wilder Department of Medicine, Division of Gastroenterology, Duke University School of Medicine , Durham, NC, USATel +1 919 668 3063Fax +1 919 668 7164 Email julius.wilder@duke.edu
                Author information
                http://orcid.org/0000-0001-7962-2053
                Article
                180161
                10.2147/TCRM.S180161
                6930514
                31908464
                43bd0cda-d64e-47c7-b602-f96665c45529
                © 2019 Spiritos et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 04 April 2019
                : 14 September 2019
                Page count
                Figures: 1, Tables: 3, References: 24, Pages: 9
                Categories
                Review

                Medicine
                acute porphyria,acute intermittent porphyria,hepatic porphyria
                Medicine
                acute porphyria, acute intermittent porphyria, hepatic porphyria

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