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1.
Sci Rep ; 11(1): 9601, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953217

RESUMO

Congenital erythropoietic porphyria (CEP) is a rare genetic disorder leading to accumulation of uro/coproporphyrin-I in tissues due to inhibition of uroporphyrinogen-III synthase. Clinical manifestations of CEP include bone fragility, severe photosensitivity and photomutilation. Currently there is no specific treatment for CEP, except bone marrow transplantation, and there is an unmet need for treating this orphan disease. Fluorescent porphyrins cause protein aggregation, which led us to hypothesize that uroporphyrin-I accumulation leads to protein aggregation and CEP-related bone phenotype. We developed a zebrafish model that phenocopies features of CEP. As in human patients, uroporphyrin-I accumulated in the bones of zebrafish, leading to impaired bone development. Furthermore, in an osteoblast-like cell line, uroporphyrin-I decreased mineralization, aggregated bone matrix proteins, activated endoplasmic reticulum stress and disrupted autophagy. Using high-throughput drug screening, we identified acitretin, a second-generation retinoid, and showed that it reduced uroporphyrin-I accumulation and its deleterious effects on bones. Our findings provide a new CEP experimental model and a potential repurposed therapeutic.


Assuntos
Acitretina/uso terapêutico , Desenvolvimento Ósseo/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Porfiria Eritropoética/tratamento farmacológico , Uroporfirinas/metabolismo , Acitretina/farmacologia , Animais , Osso e Ossos/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Porfiria Eritropoética/genética , Porfiria Eritropoética/metabolismo , Uroporfirinas/genética , Peixe-Zebra
2.
Blood ; 136(21): 2457-2468, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32678895

RESUMO

Congenital erythropoietic porphyria (CEP) is an inborn error of heme synthesis resulting from uroporphyrinogen III synthase (UROS) deficiency and the accumulation of nonphysiological porphyrin isomer I metabolites. Clinical features are heterogeneous among patients with CEP but usually combine skin photosensitivity and chronic hemolytic anemia, the severity of which is related to porphyrin overload. Therapeutic options include symptomatic strategies only and are unsatisfactory. One promising approach to treating CEP is to reduce the erythroid production of porphyrins through substrate reduction therapy by inhibiting 5-aminolevulinate synthase 2 (ALAS2), the first and rate-limiting enzyme in the heme biosynthetic pathway. We efficiently reduced porphyrin accumulation after RNA interference-mediated downregulation of ALAS2 in human erythroid cellular models of CEP disease. Taking advantage of the physiological iron-dependent posttranscriptional regulation of ALAS2, we evaluated whether iron chelation with deferiprone could decrease ALAS2 expression and subsequent porphyrin production in vitro and in vivo in a CEP murine model. Treatment with deferiprone of UROS-deficient erythroid cell lines and peripheral blood CD34+-derived erythroid cultures from a patient with CEP inhibited iron-dependent protein ALAS2 and iron-responsive element-binding protein 2 expression and reduced porphyrin production. Furthermore, porphyrin accumulation progressively decreased in red blood cells and urine, and skin photosensitivity in CEP mice treated with deferiprone (1 or 3 mg/mL in drinking water) for 26 weeks was reversed. Hemolysis and iron overload improved upon iron chelation with full correction of anemia in CEP mice treated at the highest dose of deferiprone. Our findings highlight, in both mouse and human models, the therapeutic potential of iron restriction to modulate the phenotype in CEP.


Assuntos
Anemia Hemolítica/tratamento farmacológico , Deferiprona/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Transtornos de Fotossensibilidade/tratamento farmacológico , Porfiria Eritropoética/tratamento farmacológico , 5-Aminolevulinato Sintetase/antagonistas & inibidores , 5-Aminolevulinato Sintetase/biossíntese , 5-Aminolevulinato Sintetase/genética , Adulto , Anemia Hemolítica/etiologia , Animais , Sistemas CRISPR-Cas , Linhagem Celular , Linhagem Celular Tumoral , Modelos Animais de Doenças , Células Eritroides/efeitos dos fármacos , Células Eritroides/metabolismo , Feminino , Técnicas de Introdução de Genes , Humanos , Ferro/metabolismo , Sobrecarga de Ferro/etiologia , Leucemia Eritroblástica Aguda/patologia , Camundongos , Células-Tronco de Sangue Periférico/efeitos dos fármacos , Células-Tronco de Sangue Periférico/metabolismo , Transtornos de Fotossensibilidade/etiologia , Porfiria Aguda Intermitente/metabolismo , Porfiria Eritropoética/complicações , Porfirinas/biossíntese , Interferência de RNA , RNA Interferente Pequeno/farmacologia
3.
Sci Transl Med ; 10(459)2018 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-30232228

RESUMO

Congenital erythropoietic porphyria is a rare autosomal recessive disease produced by deficient activity of uroporphyrinogen III synthase, the fourth enzyme in the heme biosynthetic pathway. The disease affects many organs, can be life-threatening, and currently lacks curative treatments. Inherited mutations most commonly reduce the enzyme's stability, altering its homeostasis and ultimately blunting intracellular heme production. This results in uroporphyrin by-product accumulation in the body, aggravating associated pathological symptoms such as skin photosensitivity and disfiguring phototoxic cutaneous lesions. We demonstrated that the synthetic marketed antifungal ciclopirox binds to the enzyme, stabilizing it. Ciclopirox targeted the enzyme at an allosteric site distant from the active center and did not affect the enzyme's catalytic role. The drug restored enzymatic activity in vitro and ex vivo and was able to alleviate most clinical symptoms of congenital erythropoietic porphyria in a genetic mouse model of the disease at subtoxic concentrations. Our findings establish a possible line of therapeutic intervention against congenital erythropoietic porphyria, which is potentially applicable to most of deleterious missense mutations causing this devastating disease.


Assuntos
Ciclopirox/uso terapêutico , Reposicionamento de Medicamentos , Porfiria Eritropoética/tratamento farmacológico , Sítio Alostérico , Animais , Fenômenos Biofísicos , Linhagem Celular , Ciclopirox/farmacocinética , Modelos Animais de Doenças , Homeostase , Camundongos , Fenótipo , Porfiria Eritropoética/enzimologia , Porfiria Eritropoética/patologia , Uroporfirinogênio III Sintetase/antagonistas & inibidores , Uroporfirinogênio III Sintetase/química , Uroporfirinogênio III Sintetase/metabolismo
4.
Middle East Afr J Ophthalmol ; 23(1): 160-2, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26957860

RESUMO

A 27-year-old male patient was presented with foreign body sensation in both the eyes for 2 years duration and blisters followed by scarring and pigmentation in the photo-exposed areas of the body over the previous 12 years. His urine was reddish colored for the previous year. On examination, there was scarring, hyper-pigmentation of photo-exposed parts of the body along with resorption of the distal phalanges of fingers in both hands except the smallest digit which had onycholysis. Ocular examination indicated scleral necrosis in the interpalpebral areas in both eyes and bilateral dry eye. Hematological examination indicated a picture suggestive of hemolytic anemia. Abdominal ultrasonography indicated an enlarged spleen. These clinical features are suggestive of puberty onset congenital erythropoietic porphyria with ophthalmological manifestations.


Assuntos
Doenças da Túnica Conjuntiva/diagnóstico , Síndromes do Olho Seco/diagnóstico , Porfiria Eritropoética/diagnóstico , Puberdade , Esclera/patologia , Maturidade Sexual , Adulto , Doenças da Túnica Conjuntiva/tratamento farmacológico , Ciclosporina/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Necrose , Soluções Oftálmicas , Porfiria Eritropoética/tratamento farmacológico , Esclera/efeitos dos fármacos
6.
Blood ; 126(2): 257-61, 2015 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-25972160

RESUMO

Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder of heme synthesis characterized by reduced activity of uroporphyrinogen III synthase and the accumulation of nonphysiologic isomer I porphyrin metabolites, resulting in ineffective erythropoiesis and devastating skin photosensitivity. Management of the disease primarily consists of supportive measures. Increased activity of 5-aminolevulinate synthase 2 (ALAS2) has been shown to adversely modify the disease phenotype. Herein, we present a patient with CEP who demonstrated a remarkable improvement in disease manifestations in the setting of iron deficiency. Hypothesizing that iron restriction improved her symptoms by decreasing ALAS2 activity and subsequent porphyrin production, we treated the patient with off-label use of deferasirox to maintain iron deficiency, with successful results. We confirmed the physiology of her response with marrow culture studies.


Assuntos
Benzoatos/uso terapêutico , Eritropoese/efeitos dos fármacos , Quelantes de Ferro/uso terapêutico , Deficiências de Ferro , Porfiria Eritropoética/tratamento farmacológico , Tolerância a Radiação/efeitos dos fármacos , Triazóis/uso terapêutico , Adulto , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células Cultivadas , Deferasirox , Evolução Fatal , Feminino , Humanos , Lactente , Luz/efeitos adversos , Uso Off-Label , Porfiria Eritropoética/genética , Porfiria Eritropoética/metabolismo , Porfiria Eritropoética/patologia , Irmãos
7.
Skin Pharmacol Physiol ; 28(2): 103-13, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25402764

RESUMO

UNLABELLED: Afamelanotide is an α-melanocyte-stimulating hormone (α-MSH) agonist with proven efficacy in photodermatoses such as erythropoietic protoporphyria (EPP). This peptide drug, repeatedly administered over prolonged time, may induce anti-drug antibodies (ADA). Here, we describe a new ELISA method developed to monitor the occurrence of ADA against afamelanotide as well as against α-MSH. Covalent binding instead of absorption of antigen onto the microtitre wells prevented antigen leakage and enabled extensive washings followed by lower background. The cut-off between antibody-negative and -positive sera was determined. Inhibition of the antigen-antibody reaction by excess soluble antigen tested for specificity. The sensitivity of the ELISA was 608 and 1,390 ng/ml of specific ADA against afamelanotide and α-MSH, respectively. This ELISA method enabled us to investigate the occurrence of ADA during long-term administration of afamelanotide. No immunoreactivity was found in 23 of the 26 EPP patients exposed to the drug for up to 6 years. Pre-existing immunoreactivity against afamelanotide as well as α-MSH was found in 3 patients, whose titres did not change during afamelanotide administration. CONCLUSION: The new ELISA is suitable to determine ADA against afamelanotide and α-MSH. Afamelanotide did not elicit ADA during long-term administration in patients with EPP.


Assuntos
Anticorpos/sangue , Ensaio de Imunoadsorção Enzimática , Porfiria Eritropoética/tratamento farmacológico , Porfiria Eritropoética/imunologia , alfa-MSH/análogos & derivados , Ensaios de Uso Compassivo , Implantes de Medicamento , Humanos , Porfiria Eritropoética/sangue , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do Tratamento , alfa-MSH/administração & dosagem , alfa-MSH/imunologia , alfa-MSH/uso terapêutico
8.
Proc Natl Acad Sci U S A ; 110(45): 18238-43, 2013 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-24145442

RESUMO

Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder characterized by uroporphyrinogen III synthase (UROS) deficiency resulting in massive porphyrin accumulation in blood cells, which is responsible for hemolytic anemia and skin photosensitivity. Among the missense mutations actually described up to now in CEP patients, the C73R and the P248Q mutations lead to a profound UROS deficiency and are usually associated with a severe clinical phenotype. We previously demonstrated that the UROS(C73R) mutant protein conserves intrinsic enzymatic activity but triggers premature degradation in cellular systems that could be prevented by proteasome inhibitors. We show evidence that the reduced kinetic stability of the UROS(P248Q) mutant is also responsible for increased protein turnover in human erythroid cells. Through the analysis of EGFP-tagged versions of UROS enzyme, we demonstrate that both UROS(C73R) and UROS(P248Q) are equally destabilized in mammalian cells and targeted to the proteasomal pathway for degradation. We show that a treatment with proteasomal inhibitors, but not with lysosomal inhibitors, could rescue the expression of both EGFP-UROS mutants. Finally, in CEP mice (Uros(P248Q/P248Q)) treated with bortezomib (Velcade), a clinically approved proteasome inhibitor, we observed reduced porphyrin accumulation in circulating RBCs and urine, as well as reversion of skin photosensitivity on bortezomib treatment. These results of medical importance pave the way for pharmacologic treatment of CEP disease by preventing certain enzymatically active UROS mutants from early degradation by using proteasome inhibitors or chemical chaperones.


Assuntos
Modelos Moleculares , Porfiria Eritropoética/tratamento farmacológico , Inibidores de Proteassoma/uso terapêutico , Uroporfirinogênio III Sintetase/genética , Uroporfirinogênio III Sintetase/metabolismo , Animais , Western Blotting , Ácidos Borônicos/farmacologia , Ácidos Borônicos/uso terapêutico , Bortezomib , Dicroísmo Circular , Primers do DNA/genética , Células Eritroides/metabolismo , Humanos , Camundongos , Mutação de Sentido Incorreto/genética , Porfiria Eritropoética/genética , Porfirinas/sangue , Porfirinas/urina , Dobramento de Proteína , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real , Espectrometria de Fluorescência , Uroporfirinogênio III Sintetase/química
9.
J Pharm Biomed Anal ; 75: 192-8, 2013 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-23277150

RESUMO

The tridecapeptide afamelanotide (Scenesse®) is a congener of α-melanocyte stimulating hormone (α-MSH). Upon binding to the melanocortin 1 receptor (MC1R) on the surface of pigment cells of the skin, the melanocytes, α-MSH or afamelanotide trigger the synthesis of cAMP, which stimulates the synthesis of melanin and therefore induces skin tanning. In a recent trial, afamelanotide administered as controlled release implants protected erythropoietic protoporphyria (EPP) patients from sunlight induced phototoxic skin reactions. Administration of biological therapeutic peptides may elicit unwanted immunogenic responses in recipients of these products. Although in a previous study using ELISA technique we excluded any newly developed immunogenicity during prolonged exposure to afamelanotide, we confirmed the previously published existence of low titers of antibodies against α-MSH in drug-naïve individuals that cross-reacted with afamelanotide. In order to investigate whether such antibodies are neutralizing, i.e. could block the biological effect of afamelanotide, we developed a cell culture-based bioassay. The basis of our assay was the measurement of afamelanotide-induced cAMP formation in a strain of the B16 mouse melanoma cell line, G4F-7, expressing the transfected human MC1R. Average half-effective concentrations of the natural hormone α-MSH and its congener afamelanotide were 38.8 ± 10.6 and 10.9 ± 7.17 nM (n=5), respectively. Neutralizing antibodies would reduce the cAMP formation. Two neutralizing anti-α-MSH antibodies served as positive controls. cAMP formation in the G4F-7 cells after addition of sera of drug-naïve (n=6) and of drug-exposed EPP patients (n=17) was significantly lower than after that from healthy volunteers (n=13). There was no difference between drug-naïve and drug-exposed patients. Using forskolin as a hormone-independent stimulator of cAMP formation, we excluded an unspecific interference of EPP sera with cAMP formation. We conclude that afamelanotide even after prolonged application to EPP patients did not elicit neutralizing antibodies. Further, the low titer immunoreactivity observed in sera of some drug-naïve individuals had no effect on the biological activity of afamelanotide.


Assuntos
Anticorpos Neutralizantes/análise , Fármacos Dermatológicos/antagonistas & inibidores , Porfiria Eritropoética/imunologia , alfa-MSH/análogos & derivados , Animais , Linhagem Celular Tumoral , Reações Cruzadas , AMP Cíclico/metabolismo , Fármacos Dermatológicos/farmacologia , Fármacos Dermatológicos/uso terapêutico , Humanos , Hipopigmentação/etiologia , Hipopigmentação/prevenção & controle , Melanócitos/efeitos dos fármacos , Melanócitos/imunologia , Melanócitos/metabolismo , Camundongos , Monitorização Imunológica , Concentração Osmolar , Porfiria Eritropoética/sangue , Porfiria Eritropoética/tratamento farmacológico , Porfiria Eritropoética/fisiopatologia , Receptor Tipo 1 de Melanocortina/genética , Receptor Tipo 1 de Melanocortina/metabolismo , Proteínas Recombinantes/metabolismo , Sistemas do Segundo Mensageiro/efeitos dos fármacos , alfa-MSH/antagonistas & inibidores , alfa-MSH/metabolismo , alfa-MSH/farmacologia , alfa-MSH/uso terapêutico
10.
Skin Res Technol ; 18(4): 405-12, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22092997

RESUMO

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare, inherited disorder of haem biosynthesis owing to deficient ferrochelatase (FECH) and accumulation of protoporphyrin IX (PPIX). This results in acute cutaneous photosensitivity upon light exposure with production of reactive oxygen species (ROS) and ultra-weak photon emission (UPE) as a by-product. We investigated if UPE evaluated the light sensitivity in EPP patients and influence of zinc treatment. METHODS: Fourteen EPP patients took zinc sulphate (3 × 200 mg/day) during spring and summer. Using a photomultiplier (PM), UPE was measured from the buttock skin and dorsal hand before and after solar-simulated light (SUN) exposure. Blood samples were analysed routinely for plasma zinc, iron, ferritin, transferrin, haemoglobin, erythrocyte PPIX and Zn-PPIX. RESULTS: UPE in EPP patients resembled that seen in healthy individuals. Without treatment, a seasonal decrease was seen from spring to summer in four control patients. However, oral zinc treatment reduced ROS formation significantly regardless of SUN exposure. After SUN exposure, the initial burst was correlated to plasma iron and erythrocyte PPIX. During treatment, an inverse correlation was found between plasma zinc concentration and the initial burst. CONCLUSION: Measurements of UPE can be used for monitoring UVA-induced oxidative processes in vivo in the skin of EPP patients.


Assuntos
Fotometria/métodos , Transtornos de Fotossensibilidade/diagnóstico , Transtornos de Fotossensibilidade/tratamento farmacológico , Porfiria Eritropoética/diagnóstico , Porfiria Eritropoética/tratamento farmacológico , Espécies Reativas de Oxigênio/análise , Sulfato de Zinco/administração & dosagem , Administração Oral , Antioxidantes/administração & dosagem , Adstringentes/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Feminino , Humanos , Masculino , Fótons , Transtornos de Fotossensibilidade/metabolismo , Projetos Piloto , Porfiria Eritropoética/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
11.
J Biol Chem ; 286(15): 13127-33, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21343304

RESUMO

A single mutation (C73R) in the enzyme uroporphyrinogen III synthase (UROIIIS) is responsible for more than one-third of all of the reported cases of the rare autosomal disease congenital erythropoietic porphyria (CEP). CEP patients carrying this hotspot mutation develop a severe phenotype of the disease, including reduced life expectancy. Here, we have investigated the molecular basis for the functional deficit in the mutant enzyme both in vitro and in cellular systems. We show that a Cys in position 73 is not essential for the catalytic activity of the enzyme but its mutation to Arg speeds up the process of irreversible unfolding and aggregation. In the mammalian cell milieu, the mutant protein levels decrease to below the detection limit, whereas wild type UROIIIS can be detected easily. The disparate response is not produced by differences at the level of transcription, and the results with cultured cells and in vitro are consistent with a model where the protein becomes very unstable upon mutation and triggers a degradation mechanism via the proteasome. Mutant protein levels can be restored upon cell treatment with the proteasome inhibitor MG132. The intracellularly recovered C73R-UROIIIS protein shows enzymatic activity, paving the way for a new line of therapeutic intervention in CEP patients.


Assuntos
Mutação de Sentido Incorreto , Porfiria Eritropoética/enzimologia , Uroporfirinogênio III Sintetase/metabolismo , Substituição de Aminoácidos , Catálise , Linhagem Celular , Cisteína/genética , Cisteína/metabolismo , Inibidores de Cisteína Proteinase/farmacologia , Estabilidade Enzimática/efeitos dos fármacos , Estabilidade Enzimática/genética , Humanos , Leupeptinas/farmacologia , Porfiria Eritropoética/tratamento farmacológico , Porfiria Eritropoética/genética , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma , Uroporfirinogênio III Sintetase/genética
15.
Int Dent J ; 55(2): 61-6, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15880959

RESUMO

Porphyria is a diverse group of diseases in which the biosynthesis of heme is disrupted by either genetic defects or environmental factors. This review gives an overview of the different types of porphyria and describes possible causes, clinical signs, diagnosis and therapy. In addition, the oral manifestations of porphyria and the potential implications of the disease for dental management are discussed.


Assuntos
Doenças da Boca/etiologia , Porfiria Eritropoética/complicações , Porfirias Hepáticas/complicações , Algoritmos , Anestesia Dentária , Arginina/uso terapêutico , Vesícula/tratamento farmacológico , Vesícula/etiologia , Carboidratos/uso terapêutico , Contraindicações , Heme/biossíntese , Heme/uso terapêutico , Humanos , Doenças da Boca/tratamento farmacológico , Fotofobia/etiologia , Sintase do Porfobilinogênio/deficiência , Porfiria Eritropoética/dietoterapia , Porfiria Eritropoética/tratamento farmacológico , Porfirias Hepáticas/dietoterapia , Porfirias Hepáticas/tratamento farmacológico , Descoloração de Dente/etiologia
17.
Ter Arkh ; 75(7): 68-73, 2003.
Artigo em Russo | MEDLINE | ID: mdl-12934485

RESUMO

AIM: To characterize patients with various nosological unities [symbol: see text] of porphyria in accordance with their age, clinical symptoms, provoking factors, therapy and outcome. MATERIAL AND METHODS: Patients with acute intermittent porphyria (43), hereditary coproporphyria (8), variegate porphyria (3), porphyria cutanea tarda (7), hepatoerythropoietic porphyria (1), and hereditary erythropoietic porphyria (2) were studied. One patient was suspected of porphyria caused by deficiency of delta-aminolevulenic acid dehydrogenase. RESULTS: The patients were from the CIS. The overwhelming majority of them were young and middle-aged subjects. Rapid development of the disease and severe neurological symptoms were predominantly observed in patients with acute forms of porphyria. CONCLUSION: Early diagnosis of porphyrin metabolism disorders makes it possible to decrease abruptly the number of cases leading to severe complications, disability, and fatal outcome. The use of inexpensive methods of screening of porphyrin metabolism disorders provides a promising approach to solving this problem. These methods should be used in municipal hospitals. In addition, asymptomatic carriers of defective gene should be revealed at the preclinical stage using various methods of molecular genetic assay.


Assuntos
Porfirias/diagnóstico , Porfirinas/metabolismo , Doença Aguda , Adolescente , Adulto , Arginina/uso terapêutico , Doença Crônica , Feminino , Heme/uso terapêutico , Humanos , Inosina Difosfato/uso terapêutico , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Plasmaferese , Porfiria Aguda Intermitente/diagnóstico , Porfiria Aguda Intermitente/tratamento farmacológico , Porfiria Aguda Intermitente/etiologia , Porfiria Aguda Intermitente/metabolismo , Porfiria Eritropoética/diagnóstico , Porfiria Eritropoética/tratamento farmacológico , Porfiria Eritropoética/etiologia , Porfiria Eritropoética/metabolismo , Porfirias/tratamento farmacológico , Porfirias/etiologia , Porfirias/metabolismo
19.
Clin Exp Dermatol ; 25(5): 406-8, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11012597

RESUMO

Erythropoietic protoporphyria (EPP) is the most common of the erythropoietic porphyrias. Recent advances in diagnostic laboratory tests have led to the discovery of a number of previously undiagnosed cases. We describe a case of EPP presenting late with a purpuric eruption and discuss the pathogenesis and significance of purpura in EPP.


Assuntos
Dermatoses da Mão/etiologia , Porfiria Eritropoética/etiologia , Púrpura/etiologia , Luz Solar/efeitos adversos , Criança , Derme/patologia , Dermatoses da Mão/tratamento farmacológico , Dermatoses da Mão/patologia , Humanos , Masculino , Porfiria Eritropoética/tratamento farmacológico , Porfiria Eritropoética/patologia , Púrpura/tratamento farmacológico , Púrpura/patologia , beta Caroteno/administração & dosagem
20.
Arch. argent. dermatol ; 49(2): 49-71, mar.-abr. 1999. ilus, tab, graf
Artigo em Espanhol | BINACIS | ID: bin-15322

RESUMO

Entre agosto de 1987 y diciembre de 1996 se observaron en nuetros servicio de dermatolgía pediátrica, sobrre un total de 37.467 pacientes con consulta de primera vez, 17 niños con diagnóstico confirmado, con una prevalencia del 0,057 por ciento (1 caso de porfiria cada 2.000 consultas de primera vez). Los 17 casos se distribuyeron de la siguiente manera. Porfiria Cutánea Tarda (PCT): 9 casos (52,9 por ciento); Protoporfiria eritropoyética (PPE): 6 casos (35,3 por ciento); Porfiria Variegata (PV): 1 caso (5,9 por ciento) y Porfiria Eritropoyéctica Congénita de G³nther (PCE): 1 caso (5, 9 por ciento). Relación: PCT/PPE: 1,5:1. La distribución de frecuencia acorde a sexo y edad fue la siguiente: PCT: relación F/M: 2:1 (F= 6 casos; M= 3 casos); Edad: Rango= 3 a 12 años X= 7 años. PPE: relación F/M: 1:2 (F= 2 casos; M= 4 casos); Edad: Rango= 2 a 11 años X= 7 años. PV: 1 caso de una niña de 8 años. PEC: 1 caso de una niña de 2 meses. El diagnóstico de porfirinas en orina, plasma, eritrocitos y materia fecal y el índice de fluorescencia plasmática, acorde a su correlación clínica. Se evaluaron los antecedentes hereditarios en la mayoria de los pacientes, observándose diferentes cuadros de porfiria comprobados en los familiares, fundamentalmente en los niños portadors de PCT. Los síntomas iniciales estuvieron asociados con fenómenos de fotosensibilidad y aparición de lesiones vesico-ampollares en regiones expuetas, principalmente cara y dorso de manos. La hipertricosis fue constante en los casos de PCT. Hubo compromiso abdominal en los casos de PEC y PV y severa onicodistrofia con hipertricosis, anemia hemolítica y mal estado general en el caso de G³nther. Un caso de PCT asociado con leucemia mieloide y otro en un paciente post-transplantado renal (no diálisis). En todos los pacientes con PPE se realizaron biopsias hepáticas con resultados normales...(AU)


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Porfiria Cutânea Tardia/diagnóstico , Porfirias Hepáticas/diagnóstico , Porfiria Eritropoética/diagnóstico , S-Adenosilmetionina/uso terapêutico , Porfirias/genética , Porfirias Hepáticas/fisiopatologia , Porfirias Hepáticas/tratamento farmacológico , Porfiria Eritropoética/fisiopatologia , Porfiria Eritropoética/tratamento farmacológico , S-Adenosilmetionina/administração & dosagem , Porfirinas/urina , beta Caroteno/uso terapêutico , Cloroquina/uso terapêutico , Piridoxina/uso terapêutico , Resultado do Tratamento , Porfirias/enzimologia , Porfirias/classificação , Transtornos de Fotossensibilidade/fisiopatologia , Diagnóstico Diferencial
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