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Acute hepatic porphyria (AHP) is a rare disease with abnormal heme metabolism, and breakthroughs have been made in the treatment of this disease in recent years. In addition to conventional treatment methods, this article reviews new therapies for AHP that are in the stage of initial clinical application or are still in the research stage, including RNAi therapy, enzyme replacement therapy, genetic supplementation of DNA or mRNA, drug molecular chaperones, and glycine transporter inhibitors for reducing heme synthesis. Moreover, this article also reviews the treatment of AHP-related comorbidities and complications, such as hyponatremia and posterior reversible encephalopathy syndrome. High glucose infusion is the main treatment method for AHP in China, and the improvement in diagnosis and increased attention to rare diseases in China has promoted the development of the diagnosis and treatment of AHP, and it is expected to explore more suitable treatment methods for AHP in the Chinese population in the future.
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ABSTRACT Introduction: Variegate porphyria (VP) is a rare disease, resulting from mutation of the protoporphyrinogen oxidase (PPOX) enzyme gene, and it is characterized by cutaneous manifestations and acute neuro-visceral symptoms. Case report: We describe the case of a 21-year-old woman from Peruvian highlands. The patient came to the emergency department for abdominal pain, quadriparesis and reddish urine. The patient also presented the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), motor neuropathy and respiratory failure. These clinical features were diagnosed as consequence of a porphyria crisis. The specific diagnosis was made with an elevated urinary porphobilinogen level (185.7 mg/24hours) and genetic analysis, which showed a rare pathogenic variant of the PPOX gene (nucleotide change: c.78C>A and protein change: p.Cys26*). The patient required intensive care until the administration of specific treatment with hemin. Conclusion: We report a case of VP with a pathogenic variant in the PPOX gene.
RESUMEN Introducción: La porfiria variegada (PV) es una enfermedad rara, resultante de la mutación del gen de la enzima protoporfirinógeno oxidasa (PPOX), se caracteriza por manifestaciones cutáneas y síntomas neuroviscerales agudos. Reporte de caso: Describimos el caso de una mujer de 21 años de la sierra peruana. La paciente acudió al servicio de urgencias por dolor abdominal, cuadriparesia y orina rojiza. La paciente también presentó el síndrome de secreción inapropiada de hormona antidiurética (SIADH), neuropatía motora e insuficiencia respiratoria. Estas características clínicas fueron diagnosticadas como consecuencia de una crisis de porfiria. El diagnóstico específico se realizó con un nivel elevado de porfobilinógeno en orina (185,7 mg/24horas) y el análisis genético, evidenció un rara variante patogénica del gen PPOX (cambio de nucleótido: c.78C>A y consecuentemente cambio de proteína: p.Cys26*). La paciente requirió cuidados intensivos hasta la administración de un tratamiento específico con hemina. Conclusion: Reportamos un caso de VP con una rara variante mutagénica en el gen PPOX.
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ABSTRACT A male infant presented with progressive jaundice immediately after birth. Fecal acholia and choluria associated with extensive bullous skin lesions in his trunk, abdomen, and upper and lower limbs developed during phototherapy. Several diagnostic hypotheses were presented, including neonatal porphyria, hemochromatosis, Alagille syndrome, and neonatal lupus. A 24-hour urine sample for the dosage of urinary porphyrins was collected, showing high results (1823.6µg in 100mL). At 50 days of life, fluorescence spectroscopy using a Wood's lamp revealed simultaneous bright red fluorescence of urine-stained diapers and sample blood. A definitive diagnosis of congenital erythropoietic porphyria was made following identification of a mutation of the uroporphyrinogen synthetases III gene on genetic testing. The patient was subsequently maintained in a low light environment since then, resulting in improvement of the lesions. Congenital erythropoietic porphyria is a disease of the group of porphyrias that presents shortly after birth with blistering occurring in regions exposed to the sun or other ultraviolet light. Atrophic scars, mutilated fingers, and bright red fluorescence of the urine and teeth may also be observed. There is no specific treatment, and prophylaxis comprising a total avoidance of sunlight is generally recommended. A high degree of suspicion is required for diagnosis. An early diagnosis can lead to less damage. Here, we present the case of a newborn with congenital erythropoietic porphyria diagnosed after presenting with bullous lesions secondary to phototherapy.
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Abstract Hereditary coproporphyria (HCP) is a congenital, autosomal dominant disorder which occurs in approximately two to five people per million inhabitants, worldwide. It is a diagnostic challenge in patients with acute abdominal pain. We present the case of a 17-year-old adolescent who debuted with atypical abdominal pain with no clear etiology. Elevated urinary porphobilinogen was found, which was treated with hematin. A genetic study concluded that the adolescent was a heterozygous carrier of the c.717T>A; p.Cys239 pathogenic nonsense mutation in the CPOX gene, leading to a diagnosis of hereditary copropophyria. The available national literature has presented cases diagnosed with acute intermittent porphyria in patients with abdominal pain of unknown origin, without covering the existing classifications of hepatic porphyrias and without detailing the genetic diagnosis; thus, this case is a contribution to the national case studies. (Acta Med Colomb 2021; 46. DOI:https://doi.org/10.36104/amc.2021.1950).
ABSTRACT
Las porfirias son un grupo complejo y heterogéneo de defectos en la vía de la síntesis del hemo. La porfiria hepato eritropoyética es un subtipo muy poco frecuente y de presentación en la infancia, con compromiso cutáneo predominante. Describimos el caso clínico de una paciente de 5 años, que se presenta con lesiones cutáneas e hipertricosis, se confirma el diagnóstico por elevación de uroporfirinas en orina y secuenciación del gen UROD.
Porphyria is a complex and heterogeneous group of heme synthesis disorder. Hepato-erythropoietic porphyria is a very rare subtype that onsets in childhood, and shows predominant skin involvement. We describe the clinical case of a 5-year-old patient who showed skin lesions and hypertrichosis and whose diagnosis was confirmed due to increased uroporphyrins in urine and UROD gene sequencing
A porfiria é um grupo complexo e heterogêneo de distúrbios da síntese do grupo heme. A porfiria hepato-eritropoiética é um subtipo muito raro que se inicia na infância e mostra envolvimento predominante da pele. Descrevemos o caso clínico de uma paciente de 5 anos que apresentou lesões cutâneas e hipertricose e cujo diagnóstico foi confirmado por aumento de uroporfirinas na urina e sequenciamento do gene UROD.
Subject(s)
Humans , Female , Child, Preschool , Blister/etiology , Porphyria, Hepatoerythropoietic/complications , Porphyria, Hepatoerythropoietic/genetics , Porphyria, Hepatoerythropoietic/urine , Diabetes Mellitus, Type 1/complications , Hypertrichosis/etiology , Uroporphyrinogen Decarboxylase/analysis , Uroporphyrins/urine , Blister/drug therapy , Coproporphyrins/urine , Hypertrichosis/drug therapyABSTRACT
RESUMEN Las porfirias son trastornos metabólicos hereditarios causados por deficiencias enzimáticas de la biosíntesis del grupo HEM. Con presentación en distintos grupos de edades, más común en infancia y tercera a cuarta década de la vida, se caracterizan por elevación de porfirinas, y manifestaciones variadas cutáneas y neuro viscerales. Describimos una serie de 3 casos de pacientes femeninas en tercera década de la vida con dolor abdominal severo e inespecífico y una amplia gama de manifestaciones clínicas con sus complicaciones a corto y largo plazo en quienes se diagnosticó porfiria aguda intermitente (PAI). Se hará revisión en la literatura para aportar al reconocimiento temprano de estas condiciones e instaurar de forma temprana el manejo específico e impactar en desenlaces irreversibles.
ABSTRACT Porphyrias are inherited metabolic disorders caused by enzymatic deficiencies of HEM group biosynthesis. Most common in childhood at the third and fourth decade of life. They are characterized by increased levels of porphyrins, and various cutaneous, neurological, and visceral manifestations. We describe a series of 3 cases of female patients in the third decade of life with abdominal pain and a wide range of clinical manifestations and short and long-term complications. Our review contributes to the early recognition of these diseases to establish early specific managements to impact on irreversible outcomes.
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ABSTRACT Background: Acute hepatic porphyrias represent an expanding group of complex inherited metabolic disorders due to inborn errors of metabolism involving heme biosynthesis. Objective: We aimed to review the main clinical and therapeutic aspects associated with acute hepatic porphyrias. Methods: The authors provided a wide non-systematic review of current concepts and recently acquired knowledge about acute hepatic porphyrias. Results: Acute neurovisceral attacks are the most common and life-threatening presentation of this group and are often considered the main clinical manifestation by clinicians during differential diagnosis and the start of proper diagnostic work-up for acute porphyrias. However, atypical presentations with central nervous system involvement, neuropsychiatric disturbances, and some subtypes with photosensitivity usually make the definite diagnosis difficult and late. Early therapeutic interventions are essential during emergency treatment and intercritical periods to avoid recurrent severe presentations. The availability of new disease-modifying therapeutic proposals based on small interfering RNA (siRNA)-based therapies, complementary to the classic intravenous glucose infusion and hemin-based treatments, emphasizes the importance of early diagnosis and genetic counseling of patients. Conclusions: This review article highlights the main biochemical, pathophysiological, clinical, and therapeutic aspects of acute hepatic porphyrias in clinical practice.
RESUMO Introdução: As porfirias hepáticas agudas representam um grupo de doenças metabólicas hereditárias complexas em expansão, decorrentes de erros inatos do metabolismo, envolvendo a via de biossíntese do grupamento heme. Objetivo: realizar revisão dos principais aspectos clínicos e terapêuticos associados com as porfirias hepáticas agudas. Métodos: Os autores realizaram ampla revisão não-sistemática sobre conceitos atuais e conhecimentos recentemente adquiridos. Resultados: Ataques neuroviscerais agudos representam a apresentação clínica mais comum e de maior risco, e são comumente considerados como principal manifestação na prática clínica durante o diagnóstico diferencial e início apropriado da investigação diagnóstica para porfirias agudas. Entretanto, apresentações atípicas com envolvimento do sistema nervoso central, alterações neuropsiquiátricas e alguns subtipos com fotossensibilidade fazem com que o diagnóstico definitivo seja comumente difícil e tardio. As intervenções terapêuticas precoces são essenciais durante o tratamento emergencial e em período intercrítico evitando formas recorrentes graves. A disponibilidade de novas propostas terapêuticas modificadoras de doença baseadas em terapias com pequenas moléculas de RNA de interferência (siRNA) complementares aos clássicos tratamentos com infusão de glicose intravenosa e à base de hemina enfatiza a importância do diagnóstico precoce de tais pacientes e do aconselhamento genético. Conclusões: Este artigo de revisão destaca os principais aspectos bioquímicos, fisiopatológicos, clínicos e terapêuticos das porfirias hepáticas agudas na prática clínica.
Subject(s)
Porphyrias, Hepatic , Porphyria, Acute Intermittent/diagnosis , Porphyria, Acute Intermittent/therapy , RNA, Small Interfering , Neurologists , Porphobilinogen SynthaseABSTRACT
Abstract: A 63-year-old black female patient with blisters and exulcerations on the face, neck, upper limbs, and subsequent evolution with hypochromic sclerotic areas and alopecia, is reported. Chronic hepatitis C and presence of high levels of porphyrins in urine were demonstrated. There was complete remission with the use of hydroxychloroquine, photoprotection, and treatment of hepatitis. Significant sclerodermoid involvement of the skin as a manifestation of porphyria cutanea tarda secondary to hepatitis C emphasizes the importance of diagnostic suspicion regarding skin manifestation in order to indicate the appropriate therapy, and to minimize the hepatic morbidity.
Subject(s)
Humans , Female , Middle Aged , Scleroderma, Localized/etiology , Porphyria Cutanea Tarda/etiology , Porphyria Cutanea Tarda/pathology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/pathology , Scleroderma, Localized/pathology , Scleroderma, Localized/therapy , Treatment Outcome , Porphyria Cutanea Tarda/therapy , Hepatitis C, Chronic/therapy , Alopecia/etiologyABSTRACT
Resumen Introducción. La porfiria es un conjunto de enfermedades metabólicas que tienen como base fisiopatológica la acumulación de precursores tóxicos. Su similitud clínica con enfermedades como el síndrome de Guillain-Barre puede retrasar el diagnostico, aumentando la posibilidad de complicaciones. Presentación del caso. Paciente femenino quien presentó síntomas inespecíficos de porfiria y síndrome de Guillain-Barre. La mujer fue evaluada de manera integral y recibió tratamiento para ambas patologías, respondiendo de manera inusual. Conclusión. La respuesta farmacológica atípica encontrada y la relación causa-efecto entre ambas entidades se justifica a la luz de sus procesos fisiopatológicos y la respuesta inmune desencadenada por los mismos.
Abstract Introduction: Porphyria is a group of metabolic diseases whose physiopathological basis is the accumulation of toxic precursors. Its clinical similarity to diseases such as Guillain-Barré Syndrome may delay diagnosis, increasing the possibility of complications. Case presentation: Female patient who presented nonspecific symptoms of porphyria and Guillain-Barré syndrome. The woman was comprehensively assessed and treated for both conditions, and had an unusual response. Conclusion: The atypical pharmacological response found and the cause-effect relationship between both entities is explained by their physiopathological processes and the immune response triggered by them.
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RESUMEN Objetivo: Las porfirias son trastornos que resultan de un defecto enzimático específico en la vía bioquímica de las porfirias. Los síntomas clínicos incluyen dolor abdominal, alteraciones gastrointestinales y manifestaciones psiquiátricas. Material y métodos: Mujer de 41 años, con diabetes gestacional y parto por cesárea hace 7 días, que acude a urgencias con convulsiones tónicoclónicas. En tratamiento antibiótico por infección de la herida quirúrgica. Los exámenes de laboratorio demostraron hiponatremia, hipokalemia y anemia. El diagnóstico de porfiria aguda intermitente (PAI) fue confirmado por el hallazgo de porfirinas elevadas en orina. La paciente fue dada de alta después de dos semanas. Resultados: se solicita un test rápido de PBG cuantitativo en orina, que resulta positivo (>10 mg PBG / g creatinina), por lo que se solicita un estudio completo de la enfermedad y se envían muestras a un hospital de referencia para análisis bioquímico y genético de PBGD/HMBS (Hidroximetilbilano sintetasa /PBG-desaminasa). Presenta la mutación c.815_818 del AGGA, que se trasmite de forma autosómica dominante, aunque con baja penetrancia. Conclusión: El diagnóstico de PAI es complejo debido al amplio espectro de síntomas, además el embarazo y el puerperio puede exacerbar la enfermedad.
SUMMARY Objective: Porphyrias are a heterogeneous group of either inherited or acquired disorders of the enzymatic biosynthesis of porphyrins. In these diseases, specific abnormalities of enzymes cause diverse clinical manifestations including abdominal pain, gastrointestinal alterations and psychiatric manifestations. Materials and methods: A 41-year-old woman with gestational diabetes and cesarean delivery 7 days ago with intradural anesthesia. She was admitted with tonic clonic seizures and diffuse abdominal pain. She is under antibiotic treatment for infection of the surgical wound. Laboratory exams showed hyponatremia, hypokalemia and anemia. A diagnosis of acute intermittent porphyria was confirmed with elevated porphyrinis in urine. Results: a rapid test of quantitative PBG in urine is permormed, which is positive (>10 mg PBG / g creatinin), so a complete study of the disease is requested and samples are sent to a reference hospital for biochemical and genetic analysis of PBGD / HMBS (Hydroxymethylbilane synthetase / PBG-deaminase). It presents the c.815_818 mutation of the AGGA, which is transmitted in an autosomal dominant manner, although with low penetrance. Conclusion: The diagnosis of acute intermittent porphyria is complex because of the wide spectrum of symptoms. Pregnancy or the puerperium might exacerbate the disease
Subject(s)
Humans , Female , Pregnancy , Adult , Pregnancy Complications/diagnosis , Porphyria, Acute Intermittent/diagnosis , Porphyrias/urine , Seizures/etiology , Porphyria, Acute Intermittent/complications , Porphyria, Acute Intermittent/urine , Porphyria, Acute Intermittent/therapy , Postpartum PeriodABSTRACT
ABSTRACT Introduction: Pseudoporphyria is a rare photodermatosis with characteristics similar to those of porphyria cutanea tarda, without, however, presenting abnormalities in porphyrin metabolism. Its etiology is related to chronic kidney disease, ultraviolet radiation and certain medications. The aim of the present study is to describe a case of furosemide-related pseudoporphyria in a patient with chronic kidney disease. Case description: A 76-year-old male patient with stage 4 chronic kidney disease and in continuous use of furosemide presented ulcerated lesions with peripheral erythema and central hematic crust in the legs. On a skin infection suspicion, treatment with quinolone and neomycin sulfate was initiated, without improvement. A biopsy of the lesion was performed, with histopathological examination demonstrating findings compatible with porphyria, although the patient did not present high porphyrin levels. The diagnosis of furosemide-induced pseudoporphyria was then established, with medication suspension, and there was a significant improvement of the lesions. Discussion: There are few cases of pseudoporphyria described, but it is believed that this condition is underdiagnosed, especially in patients with chronic kidney disease. Both clinical and histopathological findings closely resemble porphyria, differentiating it from normal levels of porphyrin in plasma, urine, or feces. Conclusions: Although the lesions are mostly benign, they may increase the morbidity and mortality of these patients, so a proper diagnosis and early treatment are extremely important.
RESUMO Introdução: A pseudoporfiria é uma fotodermatose rara com características semelhantes às da porfiria cutânea tardia, sem, no entanto, apresentar anormalidades no metabolismo da porfirina. Sua etiologia está relacionada a doença renal crônica, radiação ultravioleta e determinados medicamentos. O objetivo do presente trabalho é descrever um caso de pseudoporfiria relacionada a furosemida em paciente portador de doença renal crônica. Descrição do caso: Paciente masculino, 76 anos, com doença renal crônica estágio 4 e em uso contínuo de furosemida, apresentou lesões ulceradas com eritema periférico e crosta hemática central nas pernas. Por suspeita de infecção de pele, foi iniciado tratamento com quinolona e sulfato de neomicina, sem melhora. Foi realizada então biópsia da lesão, com exame histopatológico demonstrando achados compatíveis com porfiria, sem, no entanto, o paciente apresentar níveis elevados de porfirinas. Foi então estabelecido o diagnóstico de pseudoporfiria induzida por furosemida, com suspensão de medicação , e houve melhora significativa das lesões. Discussão: Há poucos casos de pseudoporfiria descritos, mas acredita-se que essa condição seja subdiagnosticada, principalmente em pacientes com doença renal crônica. Tanto achados clínicos quanto histopatológicos se assemelham muito à porfiria, diferenciando desta por níveis normais de porfirina no plasma, na urina ou nas fezes. Conclusões: Embora as lesões sejam majoritariamente benignas, podem aumentar a morbimortalidade desses pacientes, por isso um diagnóstico adequado e tratamento precoce são de extrema importância.
Subject(s)
Humans , Male , Aged , Porphyria Cutanea Tarda/chemically induced , Diuretics/adverse effects , Furosemide/adverse effects , Diuretics/therapeutic use , Renal Insufficiency, Chronic/drug therapy , Furosemide/therapeutic useABSTRACT
Porphyria cutanea tarda (PCT) is the most common type of porphyria: it is characterized by blistering lesions, erosions and crusts on the back of the hands, associated with photosensitivity and facial hypertrichosis. It is produced by acquired or hereditary deficiency of the enzyme UROD, fifth enzyme in the chain of production of the Heme group. This causes accumulation of porphyrins in the liver, which are subsequently mobilized to the skin, where lesions are generated by photosensitivity. This deficiency can be exacerbated by multiple causes. We report a 51-year-old female presenting with the characteristic dermal lesions described above, which disappeared when she discontinued her hormone replacement therapy with estradiol and dydrogesterone. Urinary and blood uroporphyrin and hexacarboxyl porphyrins were elevated and plasma ferritin was 479 ng/ml. Hormone replacement therapy was discontinued and phlebotomies were attempted but not tolerated by the patient. The dermic lesions have not relapsed.
Subject(s)
Humans , Female , Middle Aged , Porphyria Cutanea Tarda/diagnosis , Porphyria Cutanea Tarda/chemically induced , Hormone Replacement Therapy/adverse effects , Dydrogesterone/adverse effects , Estradiol/adverse effectsABSTRACT
A prática clínica do dermatologista baseia-se na análise das lesões cutâneas. Essa análise é feita essencialmente pela observação clínica, e atualmente complementada com exames como a dermatoscopia e a microscopia confocal. Apesar de seu baixo custo, a lâmpada de Wood tem sido cada vez menos utilizada como método diagnóstico auxiliar. Apresentamos diversos casos de utilização da lâmpada de Wood sendo de grande auxílio ao dermatologista. Esperamos assim incentivar o uso desse aparelho na prática diária.
The dermatologist's clinical practice is based on the analysis of cutaneous lesions that is carried out mainly by clinical observation, and currently supplemented with tests such as dermoscopy and confocal microscopy. Despite its low cost, the Wood's lamp has been decreasingly used as an auxiliary diagnostic method. The authors of the present study describe several cases of use of the Wood's lamp where it provided valuable assistance to the dermatologist, aiming at encouraging the use of this device in the daily practice.
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Resumen La porfiria intermitente aguda (PIA) es una enfermedad poco frecuente, considerada huérfana, que se caracteriza por crisis neuroviscerales, el dolor abdominal siendo su síntoma más común, acompañado en muchos casos, de síntomas inespecíficos, haciendo difícil su diagnóstico temprano. El retraso en el diagnóstico y tratamiento de esta entidad puede resultar catastrófico o incluso fatal, provocando daño neurológico a largo plazo o permanente. Reportamos el caso de un adulto joven que consulta en varias ocasiones por dolor abdominal inespecífico y 24 horas después de la admisión desarrolla inestabilidad autonómica simpática con cifras tensionales elevadas y taquicardia. Posteriormente debilidad muscular que evoluciona hasta cuadriplejia e hiponatremia con criterios para secreción inadecuada de hormona antidiurética (SIADH). Estos datos, junto con coloración rojiza en orina, llevan al diagnóstico de porfiria. Presentamos las características clínicas y bioquímicas enfatizando la importancia de incluir la porfiria dentro de los diagnósticos diferenciales de dolor abdominal y disautonomia de causa indeterminada. (Acta Med Colomb 2017; 42: 140-143).
Abstract Acute intermittent porphyria (AIP) is an infrequent and considered orphan disease, characterized by neurovisceral crisis, being abdominal pain the most common symptom, accompanied in many cases by non-specific symptoms, making early diagnosis difficult. The delay in the diagnosis and treatment of this entity can be catastrophic or even fatal, causing long-term or permanent neurological damage. The case of a young adult who attends medical consultation several times for non-specific abdominal pain and 24 hours after admission develops sympathetic autonomic instability with elevated blood pressure and tachycardia is presented. He subsequently presents muscular weakness that evolves to quadriplegia and hyponatremia with criteria for inadequate secretion of antidiuretic hormone (SIADH). These data together with reddish urine staining lead to the diagnosis of porphyria. The clinical and biochemical characteristics emphasizing the importance of including porphyria within the differential diagnoses of abdominal pain and dysautonomia of indeterminate cause are presented. (Acta Med Colomb 2017; 42: 140-143).
Subject(s)
Humans , Male , Adult , Porphyrias , Quadriplegia , Porphyria, Acute Intermittent , Primary Dysautonomias , Inappropriate ADH SyndromeABSTRACT
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, ErythropoieticABSTRACT
Porfirias são transtornos metabólicos de origem genética e caráter autossômico dominante ou recessivo que causam erros na rota da biossíntese das porfirinas e do grupo heme. Dentro desse grupo se destaca a porfiria aguda intermitente como sendo a mais comum entre os demais tipos de porfirias na maioria dos países, com incidência de aproximadamente 1 a 2/100.000 habitantes. Possui caráter autossômico dominante e prevalece no sexo feminino durante o período da menacme. É uma doença que tem como principais sintomas dor abdominal, náuseas, vômitos, alterações do hábito intestinal, taquicardia, febre, neuropatia periférica e distúrbios psiquiátricos. Diversos fatores podem desencadear uma crise, entre eles dieta hipocalórica e pobre em carboidratos, drogas porfirinogênicas, estresse e exercício físico extenuante. O diagnóstico precoce e tratamento adequado melhoram o prognóstico e evitam maiores complicações e a atuação do fisioterapeuta é importante na recuperação da funcionalidade corporal e na melhora da qualidade de vida do paciente. Este trabalho se baseou em uma ampla revisão bibliográfica, com base nos bancos de dados Pubmed, Lilacs e SciELO, acerca do conhecimento científico sobre porfiria aguda intermitente, bem como sua fisiopatologia, diagnóstico diferencial, prevenção, tratamento e recursos adjuvantes como a fisioterapia.
ABSTRACT
A doença de Günther ou porfiria eritropoiética congênita é uma desordem autossômica recessiva. Causada por um defeito na enzima uroporfirinogênio III sintase, leva a um acúmulo de isômeros não fisiológicos e patogênicos da porfirina. As manifestações clínicas da doença incluem eritrodontia, hipertricose, fragilidade óssea, complicações oculares, anemia hemolítica e fotossensibilidade extrema. Apesar da escassa literatura científica atualizada sobre a doença de Günther, realizou-se esta revisão bibliográfica com a finalidade de descrever pontos importantes da etiologia, diagnóstico, prognóstico, tratamento e prevenção dessa patologia. Foram consultadas as bases de dados Pubmed, Lilacs e SciELO determinando as buscas pelas palavras-chaves: porfiria eritropoiética, porfirias, porfiria cutânea tardia, porfiria variegata, porfiria hepatoeritropoiética e erros inatos do metabolismo. Pacientes com a doença de Günther podem apresentar as piores manifestações cutâneas de todas as porfirias, isso se dá devido ao aumento de porfirinas lipossolúveis que se depositam na pele. Na idade adulta os pacientes podem desenvolver osteólise severa, ressorção de falanges terminais, contraturas e outras deformidades. A deficiência de vitamina D, decorrente da não exposição ao sol, pode contribuir para tais anormalidades na estrutura do osso. Manifestações oculares incluem conjuntivite, blefarite, fotofobia, cataratas, perda de cílios e sobrancelhas e cicatriz na córnea, o que pode levar à cegueira. A doença de Günther apresenta uma variabilidade clínica considerável. Embora os tratamentos disponíveis sejam limitados, o prognóstico nem sempre é desfavorável.
ABSTRACT
Porphyrias are inherited metabolic disorders resulting from a specific enzyme defect in the heme biosynthetic pathway. Porphyrias are induced by various precipitants. Clinical features include abdominal pain, neurologic manifestations, autonomic neuropathy, and mental disturbance. Diagnosis may be delayed because of variable symptoms that mimic other diseases and because of the rarity of of porphyrias. Although most patients with known porphyria can complete anesthesia and surgery safely, undiagnosed porphyric patients are in danger of porphyric crisis due to inadvertent exposure to precipitating drugs and environment. We report a case of a patient who experienced delayed emergence with neurological disturbance after general anesthesia, ultimately diagnosed as acute intermittent porphyria.
Subject(s)
Humans , Abdominal Pain , Anesthesia , Anesthesia, General , Biosynthetic Pathways , Delayed Emergence from Anesthesia , Diagnosis , Guillain-Barre Syndrome , Heme , Neurologic Manifestations , Porphyria, Acute Intermittent , Porphyrias , Spine , Wernicke EncephalopathyABSTRACT
A associação de porfiria cutânea tarda (PCT) e lúpus eritematoso sistêmico (LES) é rara. O LES, de fisiopatologia complexa e manifestações clínicas pleomórficas, assemelha-se à PCT pela fotossensibilidade. Um achado que pode diferenciar as duas doenças são as lesões cutâneas bolhosas, raras no LES, mas características da PCT. Descrevemos um caso de associação de PCT e LES e revisamos a literatura, enfatizando questões fisiopatológicas, clínicas e terapêuticas. Um dado relevante para a prática clínica concerne ao tratamento do lúpus com antimaláricos, o que pode oferecer riscos para a PCT.
The association of porphyria cutanea tarda (PCT) and systemic lupus erythematosus (SLE) is rare. Systemic lupus erythematosus, of complex pathophysiology and pleomorphic clinical manifestations, is similar to PCT regarding photosensitivity. One finding that can differentiate both diseases is the presence of cutaneous blisters, which are rare in SLE, but characteristic of PCT. We report one case of the association of PCT and SLE and revise the literature, emphasizing pathophysiological, clinical and therapeutic aspects. One relevant information for clinical practice relates to the treatment of SLE with antimalarials, which is a risk for PCT.