Acute intermittent porphyria

University of Manchester, Rheumatic Diseases Centre, Hope Hospital, Salford M6 8HD, UK.
Baillière&#x027 s Best Practice and Research in Clinical Gastroenterology (Impact Factor: 3.48). 05/2005; 19(2):235-49. DOI: 10.1016/j.bpg.2004.10.006
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Acute intermittent porphyria (AIP) is characterised by neurovisceral crises the most common clinical presentation of which is abdominal pain. It is an autosomal dominant condition with incomplete penetrance and is potentially life-threatening. The key point in management is to suspect and confirm the diagnosis as early as possible in order to treat the attack and to avoid inappropriate treatments which may exacerbate the crisis. In this chapter we briefly outline the haem biosynthetic pathway and how deficiencies in individual enzymes give rise to the different porphyrias. We then describe the clinical features and diagnosis of AIP, followed by a discussion of pathogenesis, highlighting advances in the molecular biology of AIP and introducing the debate as to whether neurovisceral crises might result from porphyrin precursor neurotoxicity or from haem deficiency. Finally we discuss management, including family screening, avoidance of triggering factors, analgesia, maintenance of a high calorie intake, and administration of haem derivatives.

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    • "; Herrick and McColl, 2005; Siegesmund et al., 2010). Nevertheless since HA has been approved for human use, it can be suggested that HA could be tested as a supplement of HAART in selected cases. "
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    ABSTRACT: Human immunodeficiency virus-1 (HIV-1) successfully escapes from host immune surveillance, vaccines and antiretroviral agents. The available antiretroviral compounds can only control viremia, but it is impossible to eliminate the virus from the organism, namely because HIV-1 provirus persists in the reservoir cells from which the virus repeatedly disseminates into new cells. Current therapeutic approaches, however, do not specifically address the stage of virus reactivation. Heme has been demonstrated as very efficient in inhibiting HIV-1 reverse transcription, while its derivative hemin ameliorated HIV-1 infection via induction of heme oxygenase-1. Normosang (heme arginate; HA) is a human hemin-containing compound used to treat acute porphyria. In this work, we studied the effects of HA in HIV-1-acutely infected T-cell lines, and in cell lines harboring either a complete HIV-1 provirus (ACH-2 cells) or an HIV-1 "mini-virus" (Jurkat clones expressing EGFP under control of HIV LTR). We demonstrate that HA inhibited HIV-1 replication during the acute infection, which was accompanied by the inhibition of reverse transcription. On the other hand, HA alone stimulated the reactivation of HIV-1 "mini-virus" and synergized with phorbol ester or TNF-α in the reactivation of HIV-1 provirus. The stimulatory effects of HA were inhibited by N-acetyl cysteine, suggesting an increased redox stress and activation of NF-κB. Further, HA induced expression of heme oxygenase-1 (HO-1) in ACH-2 cells, while HO-1 was found expressed in untreated Jurkat clones. Inhibitor of HO-1 activity, tin protoporphyrin IX, further increased HA-mediated reactivation of HIV-1 "mini-virus" in Jurkat clones, and this effect was also inhibited by N-acetyl cysteine. The stimulatory effects of HA on HIV-1 reactivation thus seem to involve HO-1 and generation of free radicals. Additionally, the effective concentrations of HA did neither affect normal T-cell activation with PMA nor induce activation of the unstimulated cells. In conclusion, HA appears to possess a combination of unique properties that could help to decrease the pool of latently infected reservoir cells, while simultaneously inhibiting HIV-1 replication in newly infected cells. Our results thus suggest a new direction to explore in treatment of HIV/AIDS disease.
    Antiviral research 12/2011; 92(3):434-46. DOI:10.1016/j.antiviral.2011.09.011 · 3.94 Impact Factor
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    • "). Disease severity varies from minor symptoms of abdominal pain to serious or frequent attacks requiring hospitalisation. Paralysis and respiratory failure are rare but potentially lethal complications , highlighting the need for early diagnosis (Herrick and McColl 2004). Symptoms very rarely develop before puberty, but there exists a few documented cases of AIP in children (Sandberg et al. 2001; Elder 1997; Hultin et al. 2003). "
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    ABSTRACT: Objective: The Norwegian Porphyria Centre routinely offers genetic counselling and predictive genetic testing in families diagnosed with porphyria. The aim of this study was to investigate the subjective experiences of adolescents and young adults who were genetically tested for acute intermittent porphyria (AIP) as minors. What were the psychosocial consequences and how were these handled? Methods: Qualitative interviews of ten Norwegians aged 16-21 years were performed and analysed based on interpretive description. All participants were initially predictively tested for AIP as minors, but three had subsequently developed manifest disease. Results: The participants considered early diagnosis and lifestyle moderation advantageous, but finding motivation for precaution was difficult. AIP inflicted few psychosocial challenges and was a small part of the participants' identity, but risk of manifest disease was, nevertheless, a cause for concern for two participants with latent AIP. The participants were content with their present level of knowledge and they felt capable of obtaining relevant information when needed. AIP was experienced as a vague condition, and participants and their relatives attributed a variety of symptoms to the disease. Conclusion and implications: Being genetically tested as a minor was experienced as useful and entailed relatively few adverse psychosocial consequences, although there was a potential for concern. Appropriate and individually tailored genetic counselling and written consent is subsequently advised. What constitutes a suitable age for testing will differ from individual to individual, but these results suggest that parents in collaboration with their children may be suited to decide what age is appropriate.
    11/2011; 1:1-7. DOI:10.1007/8904_2011_8
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    • "There are three autosomal dominant acute porphyrias: AIP, variegate porphyria, and hereditary coproporphyria. Symptomatic AIP prevalence is 2 to 3 cases per 100,000 persons per year [3]. Porphyria attacks can be triggered by environmental factors, reduced calorie intake [4], medications (barbiturate, calcium channel blockers, antibiotics, antifungals, and hormones ) [5], large alcohol intake, nicotine abuse, infection, surgery, or psychological disorder. "
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    ABSTRACT: Despite being challenging, delivery of effective nursing care to patients with acute intermittent porphyria is a matter of utmost importance. In this paper, the diversity of symptoms and the difficult diagnosis of this condition are emphasized, and details concerning the treatment of this disorder in the intensive care unit are presented. We believe that acute intermittent porphyria should be borne in mind during performance of differential diagnosis of neurological, psychiatric, and gastroenterological disorders on patients whose routine investigation tests are normal, especially when precipitating factors exist. Intensive care measures and a multidisciplinary team approach are essential.
    Critical care research and practice 05/2011; 2011(6):283690. DOI:10.1155/2011/283690
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