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1.
Hematol., Transfus. Cell Ther. (Impr.) ; 40(2): 182-188, Apr.-June 2018. ilus
Article in English | LILACS | ID: biblio-953828

ABSTRACT

ABSTRACT Hemoglobin is an essential biological component of human physiology and its production in red blood cells relies upon proper biosynthesis of heme and globin protein. Disruption in the synthesis of these precursors accounts for a number of human blood disorders found in patients. Mutations in genes encoding heme biosynthesis enzymes are associated with a broad class of metabolic disorders called porphyrias. In particular, one subtype - erythropoietic protoporphyria - is caused by the accumulation of protoporphyrin IX. Erythropoietic protoporphyria patients suffer from photosensitivity and a higher risk of liver failure, which is the principle cause of morbidity and mortality. Approximately 90% of these patients carry loss-of-function mutations in the enzyme ferrochelatase (FECH), while 5% of cases are associated with activating mutations in the C-terminus of ALAS2. Recent work has begun to uncover novel mechanisms of heme regulation that may account for the remaining 5% of cases with previously unknown genetic basis. One erythropoietic protoporphyria family has been identified with inherited mutations in the AAA+ protease ClpXP that regulates ALAS activity. In this review article, recent findings on the role of ClpXP as both an activating unfoldase and degrading protease and its impact on heme synthesis will be discussed. This review will also highlight the role of ClpX dysfunction in erythropoietic protoporphyria.


Subject(s)
Porphyrias , Protoporphyria, Erythropoietic , Endopeptidase Clp , Enzymes
2.
Acta bioquím. clín. latinoam ; 50(4): 547-573, dic. 2016. ilus, tab
Article in Spanish | LILACS | ID: biblio-837630

ABSTRACT

Las porfirias son enfermedades metabólicas consecuencia de fallas en la biosíntesis del hemo, caracterizadas por un patrón específico de acumulación y excreción de intermediarios, responsables de su patofisiología. En las porfirias agudas el exceso de ácido d-aminolevúlico (ALA) produce una sintomatología neuroabdominal asociada al daño oxidativo por formación de especies reactivas de oxígeno (ROS), originadas por autooxidaxión del ALA. En las cutáneas, la sintomatología es producto de la acumulación de porfirinas, que como el ALA, inducen la formación de ROS. Su desencadenamiento se precipita por factores endógenos (ayuno, estrés, hormonas) y/o exógenos (fármacos), en particular algunos anestésicos. Se presenta una revisión de los estudios bioquímicos y genéticos en pacientes con diferentes porfirias obtenidos en el Centro de Investigaciones de Porfirias y Porfirinas (CIPYP), durante los últimos 38 años, que permitieron ampliar el conocimiento sobre las bases moleculares sobre estas patologías. Se describen los logros resultantes del empleo de modelos experimentales de porfiria, inducida farmacológica o genéticamente, que contribuyeron a la clasificación de algunas drogas como prohibidas para pacientes con porfiria. Finalmente, las porfirinas generadoras de ROS, y por ende inductoras de muerte celular, tienen su aplicación para combatir infecciones por organismos hemo-deficientes como Trypanosoma cruzi y también para ser utilizadas como fotosensibilizadores en la terapia fotodinámica (TFD).


Porphyrias comprise a group of metabolic disorders of the heme biosynthesis pathway resulting in a specific accumulation and excretion of intermediates which are responsible for their pathophysiology. Acute porphyrias are characterized by acute neurovisceral symptoms due to the overproduction and accumulation of d-aminolevulinic acid (ALA) which leads to an oxidative damage resulting from the formation of reactive oxygen species (ROS). In cutaneous porphyrias, the symptomatology is a result of porphyrin accumulation which also induces ROS moulding. In both cases, their clinical signs are precipitated by endogenous factors (stress, hormones, low calories intake) and/or exogenous drugs, in particular some anaesthetics. A review of the biochemical and genetic results obtained from patients with different porphyrias, diagnosed at the CIPYP during the last 38 years is presented here, aimed at obtaining additional evidence about the molecular nature of these disorders. The achievements obtained from experimental porphyria models -pharmacologically or genetically induced- are also described, which contributed to the classification of some drugs as prohibited for their use in porphyric patients. Finally, as porphyrins produce ROS and therefore cellular death, they can be used to treat infections by heme-deficient organisms like Trypanosoma cruzi and also as photosensitizers in photodynamic therapy (TFD).


As Porfirias são doenças metabólicas decorrentes de falhas na biossíntese do Hemo, caracterizadas por um padrão específico de acumulação e excreção de intermediários responsáveis de sua patofisiologia. Nas Porfirias Agudas, o excesso de ácido δ-aminolevulínico (ALA) produz uma sintomatologia neuroabdominal associada ao dano oxidativo por formação de espécies reativas de oxigênio (ROS), decorrentes da auto-oxidação do ALA. Nas Cutâneas a sintomatologia é produto da acumulação de porfirinas, que como o ALA, induzem a formação de ROS. Seu desencadeamento precipita-se por fatores endógenos (jejum, estresse, hormônios) e/ou exógenos (fármacos), especialmente alguns anestésicos. Apresenta-se uma revisão dos estudos bioquímicos e genéticos em pacientes com diferentes Porfirias obtidos no Centro de Investigações de Porfirias e Porfirinas (CIPYP), durante os últimos 38 anos, que permitiram ampliar o conhecimento sobre as bases moleculares destas patologias. Descrevem-se as conquistas resultantes do uso de modelos experimentais de Porfiria, induzida farmacológica ou geneticamente, que contribuíram à classificação de algumas drogas como proibidas para pacientes com Porfiria. Afinal, as porfirinas geradoras de ROS e, por conseguinte, indutoras de morte celular têm sua aplicação para combater infecções por organismos hemo-deficientes como Trypanosoma cruzi e também ser utilizadas como fotossensibilizadores na terapia fotodinâmica (TFD).


Subject(s)
Humans , Anesthetics , Photochemotherapy , Porphyrias , Porphyrias/metabolism , Porphyrins , Trypanosoma cruzi , Porphyria, Erythropoietic , Protoporphyria, Erythropoietic
3.
Clinical and Molecular Hepatology ; : 411-415, 2012.
Article in English | WPRIM | ID: wpr-15268

ABSTRACT

Erythropoietic protoporphyria (EPP) is an inherited disorder of the heme metabolic pathway that is characterized by accumulation of protoporphyrin in the blood, erythrocytes, and tissues, and cutaneous manifestations of photosensitivity, all resulting from abnormalities in ferrochelatase (FECH) activity due to mutations in the FECH gene. Protoporphyrin is excreted by the liver, and excess protoporphyrin leads to cholelithiasis with obstructive episodes and chronic liver disease, finally progressing to liver cirrhosis. Patients with end-stage EPP-associated liver disease require liver transplantation. We describe here a 31-year-old male patient with EPP who experienced acute-on-chronic liver failure and underwent deceased-donor liver transplantation. Surgical and postoperative care included specific shielding from exposure to ultraviolet radiation to prevent photosensitivity-associated adverse effects. The patient recovered uneventfully and was doing well 24 months after transplantation. Future prevention and treatment of liver disease are discussed in detail.


Subject(s)
Adult , Humans , Male , Acute Disease , End Stage Liver Disease/etiology , Ferrochelatase/genetics , Liver Cirrhosis/diagnosis , Liver Transplantation , Mutation , Protoporphyria, Erythropoietic/complications
4.
The Korean Journal of Hepatology ; : 83-88, 2010.
Article in English | WPRIM | ID: wpr-98606

ABSTRACT

Erythropoietic protoporphyria (EPP) is a rare disorder of heme biosynthesis caused by mutations in the gene encoding the enzyme ferrochelatase. In EPP, deficient ferrochelatase activity leads to the excessive production and biliary excretion of protoporphyrin (PP). The major clinical features of EPP are photosensitivity and hepatobiliary disease that may progress to severe liver disease, that are caused by the toxicity of PP. EPP-related liver disease has been treated medically or surgically including liver transplantation. We described a 20-year-old male with severe liver disease who was diagnosed with EPP based on clinical and laboratory findings. He was treated with cholestyramine resin. Six months after the treatment, he was doing well without any abdominal pain or photosensitivity.


Subject(s)
Humans , Male , Young Adult , Bilirubin/blood , Cholestyramine Resin/therapeutic use , Edema/complications , Erythema/complications , Ferrochelatase/genetics , Liver Diseases/complications , Protoporphyria, Erythropoietic/complications , Protoporphyrins/metabolism
5.
Rev. argent. dermatol ; 87(4): 248-263, oct.-dic. 2006. ilus, tab
Article in Spanish | LILACS | ID: lil-634318

ABSTRACT

Las porfirias son consecuencia de fallas en el metabolismo del hemo. Se clasifican según el tipo de sintomatología clínica prevalente o el órgano donde se expresa preferencialmente la falla metabólica. En general la deficiencia enzimática está asociada a mutaciones en los genes que codifican para cada una de las enzimas. Están descritos 7 tipos de porfiria diferentes. Se transmiten por carácter autosómico dominante a excepción de la PCE, la PHE y la NPA que son recesivas. Sin embargo, están reportadas variantes homocigotas para el resto de las porfirias de pronóstico y evolución mucho más grave que la forma heterocigota. La descripción de estos casos poco frecuentes, sus tratamientos y evolución, facilitarían tanto el diagnóstico diferencial de la porfiria como el conocimiento de las posibilidades terapéuticas en cada caso. Asimismo para las porfirias heterocigotas con manifestación infantil, su identificación temprana y tratamiento aseguraría una mejor evolución minimizando los riesgos asociados. Se han diagnosticado 5 casos de porfirias agudas en niñas: 2 de PAI, 2 de PV y 1 de CPH. Entre las porfirias cutáneas se presentan 25 casos de PCT infantil, el primer caso de PHE en Argentina, 4 casos de PCE infantil y 1 en un adulto y 2 casos de PPE con compromiso hepatobiliar.


The Porphyrias are a group of diseases resulting from partial deficiencies in one of the heme biosynthetic enzymes. These disorders can be classified on the basis of their clinical manifestations or according the organ where the metabolic deficiency is mainly expressed. In general this enzyme deficiency is associated with mutations in the genes which codify each enzyme. There are 7 types of Porphyrias. They are autosomal dominant disorders with the exception of PCE, PHE and NPA which are recessive. However, some rare and severe cases with recessive inheritance have also been reported. The description of these infrequent cases and their treatments and evolution would make easier the differential diagnosis of Porphyrias as well as the therapeutic possibilities to be applied in each case. Moreover, it is very important the early identification and treatment of infantile heterozygous porphyrias to avoid the risks of associatedd complications. In the CIPYP we have diagnosed 5 cases of infantil Acute Porphyrias: 2 PAI, 2 PV and 1 CPH. In the group of Cutaneous Porphyrias we present 25 cases of infantil PCT, the first case of PHE in Argentina, 4 cases of infantil PCE and 1 adult PCE and 2 cases of PPE with hepatic failure.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Porphyrias/classification , Diagnosis, Differential , Argentina/epidemiology , Porphyrias/therapy , Porphyrias, Hepatic/diagnosis , Porphyria, Erythropoietic/diagnosis , Porphyria, Hepatoerythropoietic/diagnosis , Porphyria Cutanea Tarda/diagnosis , Porphyria, Acute Intermittent/diagnosis , Coproporphyria, Hereditary/diagnosis , Porphyria, Variegate/diagnosis , Protoporphyria, Erythropoietic/diagnosis
6.
Rev. Fac. Cienc. Méd. (Córdoba) ; 63(3): 9-16, 2006. tab
Article in Spanish | LILACS | ID: lil-474454

ABSTRACT

Objetivo: Correlacionar parámetros bioquímicos de hierro y desarrollo psicomotríz, en relación al origen social, en niños de 6 a 24 meses de Córdoba, Argentina. Material y Métodos: En 276 niños se determino el estado nutricional del hierro con el criterio de Hillman, combinando ferritina, hemoglobina y protoporfirina eritrocitaria, para desarrollo Escala de Bayley 11, y variables socioeconómicas. Resultados y Conclusiones: La anemia presento diferencias (p<0.05) entre los niveles soci21es, la depleción fue 42 % en la población total. El desarrollo motor fue homogéneo en los grupos sociales; mientras que el mental presento diferencias ( p< 0.05) en retraso leve y significativo, siendo los mas afectados los niños del nivel bajo. En desarrollo y parámetros bioquímicos, el 19 % de los niños con anemia y depleción, presentaron retraso motor leve, mientras que en desarrollo mental, el retraso leve y significativo afecto en doble proporción a los niños con depleción y anemia en comparación con los niños normales.


Aims: To correlate the iron biochemical screening with cognitive and motor development, related to social background, in 6 to 24 month infants. Methods: a population - based study of 276 children. The iron deficiency was determine by the modified criterion of Hillman ( 1996), combining three different screenings tests: serum ferritin, hemoglobin and erythrocyte protoporphyrin. To analyse development we used Bayley 11 Scale. Results and conclusions: the anaemia was significative different (p< 0,05) between social levels, 36% in children with low socioeconomic background, 8% for the high one and iron deficiency without anaemia 42% in the total population. The motor development was homogeneous by social groups, showed 1 % significative delay, 8% light delay. But the mental development shows significative differences (p<0,05) in both light and significative delay, been the must affected children with low socioeconomic background.


Subject(s)
Humans , Infant , Developmental Disabilities/diagnosis , Infant Nutritional Physiological Phenomena/physiology , Iron/deficiency , Poverty , Psychomotor Performance/physiology , Anemia, Iron-Deficiency/blood , Chi-Square Distribution , Developmental Disabilities/blood , Ferritins/blood , Hemoglobins/analysis , Iron/blood , Mass Screening , Protoporphyria, Erythropoietic/blood , Severity of Illness Index
7.
Korean Journal of Pediatric Gastroenterology and Nutrition ; : 263-268, 2005.
Article in Korean | WPRIM | ID: wpr-202891

ABSTRACT

Erythropoietic protoporphyria is a genetic disorder due to a deficiency of ferrochelatase resulting in excessive accumulation and excretion of protoporphyrin. The predominant clinical feature is photosensitivity. Severe hepatic failure occurs in a small percentage of patients, and neurological symptoms are very rare. We report a case of erythropoietic protoporphyria associated with severe hepatic dysfunction and neurological symptoms. A 9-year-old girl presented with severe abdominal pain, nausea, weakness and pain of extremities, and urinary retention. Ultrasonogram and abdominal CT scanning revealed a diffuse infiltrated and enlarged liver. Liver biopsy showed deposition of dense dark brown pigment within the bile, hepatocytes and Kupffer cells. Plus, dense dark brown deposits gave a red birefringent under polarize light. Porphyrin studies demonstrated markedly elevated serum free erythrocyte protoporphyrin. This girl was diagnosed as erythropoietic protoporphyria with severe liver dysfunction and neurological symptoms.


Subject(s)
Child , Female , Humans , Abdominal Pain , Bile , Biopsy , Erythrocytes , Extremities , Ferrochelatase , Hepatocytes , Hepatomegaly , Kupffer Cells , Liver Diseases , Liver Failure , Liver , Nausea , Protoporphyria, Erythropoietic , Tomography, X-Ray Computed , Ultrasonography , Urinary Retention
8.
Korean Journal of Dermatology ; : 63-67, 2002.
Article in Korean | WPRIM | ID: wpr-21208

ABSTRACT

Erythropoietic protoporphyria (EPP), caused by decreased activity of the enzyme ferrochelatase, is characterized clinically by burning photosensitivity beginning from childhood, and chemically by excessive amounts of red blood cell protoporphyrins. 1-10% of EPP patients develop potentially fatal protoporphyric hepatic failure. The diagnosis of EPP had been missed in many cases when traditional solvent extraction qualitative screening test was used for blood porphyrins, and use of fluorescence microscopy improved this problem. We report a case of EPP screened by fluorescence microscopy of erythrocytes in a 50-year-old man complaining of photosensitivity. We recommend fluorescence microscopy could be the screening test of choice for the detection of increased red blood cell porphyrins.


Subject(s)
Humans , Middle Aged , Burns , Diagnosis , Erythrocytes , Ferrochelatase , Fluorescence , Liver Failure , Mass Screening , Microscopy, Fluorescence , Porphyrins , Protoporphyria, Erythropoietic , Protoporphyrins
9.
Korean Journal of Dermatology ; : 1375-1379, 2000.
Article in Korean | WPRIM | ID: wpr-75965

ABSTRACT

Erythropoietic protoporphyria(EPP) is an inherited inborn error of porphyrin metabolism caused by decreased activity of the enzyme ferrochelatase. EPP is characterized clinically by photosensitivity to visible light commencing in childhood, and biochemically by elevated red cell free protoporphyrin levels. We report herein a case of EPP which occurred in a 44-year-old man and his family. He had suffered from immediate photosensitivity since he was 4 years old. He was presented with burning, erythema, scars and waxy thickening of the sun-exposed skin. Red cell free protoporphyrin level was elevated and urinary porphyrins were normal. Histopathologically, homogeneous eosinophilic materials that stained with PAS were deposited in perivascular area of upper dermis. He was managed with light restriction and sunscreen.


Subject(s)
Adult , Child, Preschool , Humans , Burns , Cicatrix , Dermis , Eosinophils , Erythema , Ferrochelatase , Light , Metabolism , Porphyrins , Protoporphyria, Erythropoietic , Skin
10.
Annals of Dermatology ; : 25-29, 1993.
Article in English | WPRIM | ID: wpr-143585

ABSTRACT

Erythropoietic protoporphyria (EPP) is an autosomal dominant condition due to decreased activity of ferrochelatase. The disease is characterized by a wide range of photocutaneous changes and occasionally by liver disease. The level of protoporphyin is raised in erythkocytes and it may also be increased in the feces. We report herein a case of EPP present in a family which was diagnosed by a high free erythrocyte protoporphyrin (FEP) count.


Subject(s)
Humans , Erythrocytes , Feces , Ferrochelatase , Liver Diseases , Protoporphyria, Erythropoietic
11.
Annals of Dermatology ; : 25-29, 1993.
Article in English | WPRIM | ID: wpr-143576

ABSTRACT

Erythropoietic protoporphyria (EPP) is an autosomal dominant condition due to decreased activity of ferrochelatase. The disease is characterized by a wide range of photocutaneous changes and occasionally by liver disease. The level of protoporphyin is raised in erythkocytes and it may also be increased in the feces. We report herein a case of EPP present in a family which was diagnosed by a high free erythrocyte protoporphyrin (FEP) count.


Subject(s)
Humans , Erythrocytes , Feces , Ferrochelatase , Liver Diseases , Protoporphyria, Erythropoietic
12.
Korean Journal of Dermatology ; : 817-822, 1993.
Article in Korean | WPRIM | ID: wpr-101006

ABSTRACT

Erythropoietic protoporphyria, sometimes also called erythrohepitic protoporphyria or simple protoporphyria, is a heritable detect of heme synthesis in which the last enzyme of the heme synthetic pathway, ferrochelatase(or heme synthetase), is functioning subopt,imally. A 23-year-old male has experi nced erythema and edema on the fae and hands during or immediately after sun exposure, since 3 years of age. The skin lesions have been accompanied by severe itching, a buring sensation and pain. Severe episodes were followed hy head iche and vomiting. We have seen a case of erythropoietic protoporphyria presenting clinically and histo athologically, wit.h a skin lesion on the sun exposured area, and free erthrocyte protoporphyrin serologically.


Subject(s)
Humans , Male , Young Adult , Edema , Erythema , Hand , Head , Heme , Protoporphyria, Erythropoietic , Pruritus , Sensation , Skin , Solar System , Vomiting
13.
Korean Journal of Dermatology ; : 745-751, 1982.
Article in Korean | WPRIM | ID: wpr-41274

ABSTRACT

A 26-year-old male has experienced repeated pruritic and burning erythema and edema over the exposed areas of the skin, especially on the face and hands, after sunlight exposure. He stated that his father, three aunts, and three sisters had similar sunlight sensitivity. The face showed tiny whitish scars. And also there were hypopigmented scars on the dorsum of the hands. Characteristic laboratory findings were as followa: RBC, plasma and stool fluoresced coral red color under the Woods light. 100ml of the RBC contained 245 pg of protoporphyrin. On photosensitive test using sunlight for 60 rninutes, there developed painful sensation at 4 minutes and 40 seconds after exposure, erythema at 12 minutes after, and edema at 20 minutes after. Pathological findings of the specimen obtained from erythematous lesion of the forehead revealed hypergranulosis and acanthosis in the epidermis and perivascular thickening and hyalin deposit around the capillaries in the upper dermis. For treatment, avoidance of exposure to sunlight was recomrnended and symptomatic therapy was tried.


Subject(s)
Adult , Humans , Male , Anthozoa , Burns , Capillaries , Cicatrix , Dermis , Edema , Epidermis , Erythema , Fathers , Forehead , Hand , Hyalin , Plasma , Protoporphyria, Erythropoietic , Sensation , Siblings , Skin , Sunlight , Wood
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