Acute hepatic porphyria: when to perform liver transplantation?

. (AU)Acute hepatic porphyrias (AHPs) are inborn errors of hemebiosynthesis and its most common and severe type is the acute intermittent porphyria (AIP). AIP is an hereditary autosomal dominant disease caused by accumulated porphobilinogen deaminase (PBG) and delta aminolevulin acid (ALA) products. The main symptoms are severe abdominal pain, neuromuscular and psychiatric disturbances, nausea, vomiting, encephalopathy, tachycardia, seizures, tremors and hypertension, that usually are manifested by acute crises. The treatment is based on clinical management and in cases which the patient's quality of life is affected liver transplantation (LT) may be an alternative choice. We report the case of a patient with AHP presenting recurrent crisis leading to chronic symptoms occurrence and poor quality of life with progressive unresponsiveness to hemin treatment. Patient was submitted to LT as curative therapy proposal, but patient still presents some clinical manifestations that may indicate the possibility of a secondary cause to explain persistence of her symptoms despite of biochemical normalization of ALA and PBG. (AU)

As porfirias hepáticas agudas (PHA) compreendem um grupo de porfirias que apresentam erros inatos na biossíntese do grupo heme, sendo a mais severa e o tipo mais comum da PHA, a porfiria aguda intermitente (PAI). A PAI é uma doença autossômica dominante causada pelo acúmulo dos produtos porfobilinogênio deaminase (PBG) e ácido delta-aminolevulínico (ALA). Os principais sintomas são dor abdominal intensa, distúrbios neuromusculares e psiquiátricos, náuseas, vômitos, encefalopatia, taquicardia, febre, tremores e hipertensão, os quais normalmente são manifestados durante as crises agudas. O tratamento é baseado no manejo clínico de todos pacientes durante a crise. Para os casos em que a qualidade de vida do paciente é afetada negativamente, a terapêutica de transplante hepático poderá ser indicada. O objetivo do relato de caso é introduzir o tratamento de uma paciente com recorrentes crises agudas de porfiria e danos em sua qualidade de vida. Uma vez que a paciente não apresentou melhora após tratamento com hematina, foi submetida ao transplante hepático visando a cura da doença. Após o transplante, a paciente ainda apresentou alguns sintomas clínicos, necessitando reformular uma segunda hipótese para explicar a persistência de tais sintomas apesar da normalização dos níveis de ALA e PBG. (AU)

Acute hepatic porphyrias for the neurologist: current concepts and perspectives / Porfirias hepáticas agudas para o neurologista: conceitos atuais e perspectivas

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.

Porfiria intermitente aguda: reporte de caso / Acute intermittent porphyria: A case report

El término 'porfiria' proviene del griego 'porphyra' y alude a un grupo heterogéneo de trastornos metabólicos causados por una deficiencia enzimática en la biosíntesis del grupo hemo. La causa de la porfiria intermitente aguda es la deficiencia de la enzima deaminasa del porfobilinógeno. Se presenta el caso de una mujer de 40 años que presentó dolor abdominal de 10 días de evolución, trastorno hidroelectrolítico grave debido a hiponatremia e hipopotasemia, taquicardia e hipertensión arterial sistémica persistentes, por lo cual fue sometida a una laparotomía en la que no se encontró ninguna afección de origen quirúrgico, A los siete días del examen inicial, la paciente desarrolló cuadriparesia flácida aguda y presentó una crisis convulsiva tónico-clónica generalizada. Los estudios neurofisiológicos evidenciaron una polineuropatía axonal mixta, y los valores de porfobilinógeno y porfirinas en orina eran elevados. Tras diagnosticarse porfiria intermitente aguda, esta se trató con hemina, lo que estabilizó los signos clínicos y normalizó el porfobilinógeno. La prevalencia de esta enfermedad es de 1 en 2.000 personas. Tiene un patrón de herencia autosómico dominante y se manifiesta principalmente en mujeres con edades entre los 20 y los 40 años. La enfermedad cursa con síntomas neurológicos y viscerales, y se trata con la administración de hemina y dextrosa, evitando las soluciones hipotónicas por el riesgo de exacerbar la hiponatremia.

The term 'porphyria' comes from the Greek 'porphyra'. It refers to a heterogeneous group of metabolic disorders caused by the enzymatic deficiency in the biosynthesis of the heme group. Acute intermittent porphyria is caused by a deficiency of the porphobilinogen deaminase enzyme. A 40-year-old woman presented with abdominal pain for ten days (which required laparotomy that evidenced no surgical pathology), severe hydroelectrolytic disorder due to hyponatremia and resistant hypokalemia, persistent tachycardia and hypertension. Seven days later, she developed acute flabby quadriparesis and presented a single generalized tonic-clonic convulsive crisis. Neurophysiological studies supported mixed axonal polyneuropathy and urine results of porphobilinogen and porphyrins were elevated. After acute intermittent porphyria was diagnosed, hemin was administered, which stabilized the patient's clinical signs and normalized the porphobilinogen. The prevalence of this entity is 1 in 2,000 people. It is an autosomal dominant disease, which affects mainly women between 20 and 40 years of age. This entity manifests with neurological and visceral symptoms. Management consists of hematin and dextrose administration avoiding hypotonic solutions because of the risk of exacerbating hyponatremia.

Porfirias agudas: manifestaciones inespecíficas y manejo terapéutico inespecíficas y manejo terapéutico específico / Acute porphyrias: non-specific manifestations and specific therapeutic management specific therapeutic management

Revisión clínica, científica, teórica y documental teniendo como objetivo principal realizar una revisión sobre la porfiria aguda, su enfoque, diagnóstico y tratamiento. Se utilizó una metodología descriptiva, cualitativa y teórica que permitió la revisión bibliográfica de los estudios relacionados con la porfiria aguda, trastorno congénito poco frecuente que causa alteraciones en las enzimas de la biosíntesis del grupo hem. La importancia de esta patología radica en que se confunde con otras enfermedades debido al cuadro clínico complejo difícil de identificar, lo que ocasiona un diagnóstico tardío que puede comprometer la vida del paciente y por ello se conoce como enfermedad silenciosa. Como conclusión se recomienda mayor atención a los factores precipitantes de los ataques agudos por la elevada morbimortalidad, así como hacer un diagnóstico rápido y oportuno por medios cualitativos y cuantitativos solicitando PBG (porfobilinógeno) y ALA (ácido delta aminolevulínico).

This was a clinical, scientific, theoretical and documental review aimed to conduct a revision on the approach, diagnosis and treatment of acute porphyria. A descriptive, quantitative and theoretical methodology was used, allowing a bibliographic review of the studies on acute porphyria, an unusual congenital disorder characterized by the deficiency of specific enzymes involved in the heme group biosynthesis. This disease importance lies on being confused with other conditions due to its complex clinical manifestations leading to a delayed diagnosis which may become life-threatening thus it is known as a silent disease In conclusion, identifying the precipitating factors of acute attacks for its high morbidity and mortality, as well as achieving a rapid and timely diagnosis by using a quantitative or qualitative determination of PBG (porphobilinogen)) and ALA (delta-aminolevulinic acid) levels, deserve special attention.

Porfiria aguda intermitente con debut en el puerperio / Acute intermittent porphyria with debut in the puerperium

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

Trastornos psiquiátricos secundarios a enfermedades neurometabólicas / Psychiatric Disorders Secondary to Neurometabolic Disorders

Hay algunas enfermedades secundarias a errores innatos del metabolismo que se asocian a trastornos psiquiátricos o síntomas neurológicos menores. La existencia de algunos pacientes con signos únicamente psiquiátricos representa un desafío diagnóstico y terapéutico. El objetivo del presente artículo es describir 6 enfermedades neurometabólicas tratables que se presentan con síntomas psiquiátricos que camuflan su origen orgánico, con el propósito de que se las tome en cuenta en la consulta psiquiátrica. Se describen los trastornos del metabolismo de la homocisteína y del ciclo de la urea, la enfermedad de Wilson, la enfermedad de Niemann-Pick tipo C, la porfiria aguda y la xantomatosis cerebrotendinosa. El análisis de la literatura lleva a proponer una lista de síntomas psiquiátricos asociados con dichas afecciones, que abarcan desde los cambios insidiosos del afecto y el curso del pensamiento hasta síntomas atípicos, como alucinaciones visuales, efectos paradójicos de los medicamentos antipsicóticos y trastornos del comportamiento de niños y adolescentes que conllevan degradación de la autonomía. Asimismo se listan los signos neurológicos más frecuentemente relacionados, como las alteraciones del estado de conciencia, los trastornos de la conducta motora y el equilibro, la catatonia o el déficit cognitivo progresivo. Se hace hincapié en la importancia de considerar la resistencia al tratamiento antipsicótico como una señal importante para sospechar organicidad y la mejoría significativa de la alteración psiquiátrica cuando se instaura un tratamiento eficaz y precoz.

Some diseases secondary to inborn errors of metabolism are associated with psychiatric, disorders or minor neurological symptoms. The existence of some cases with exclusively psychiatric symptoms represents a diagnostic and therapeutic challenge. The aim of this article is to describe seven treatable neurometabolic disorders that should be taken into account in the psychiatric consultation as they manifest with psychiatric symptoms that mask the organic origin of the disorder. Homocysteine metabolism and urea cycle disorders, Wilson's disease, Niemann-Pick disease Type C, acute porphyria and cerebrotendinous xanthomatosis are described. Following an analysis of the literature, a list of psychiatric symptoms associated with these disorders are proposed, ranging from insidious changes in affective state and thought to atypical symptoms such as visual hallucinations, as well as paradoxical effects of antipsychotics or behavioural disorders in children and adolescents associated with loss of autonomy. The most frequently associated neurological signs, such as alterations in the state of consciousness, motor behaviour and balance disorders, catatonia or progressive cognitive deficit are also listed. Emphasis is placed on the importance of considering resistance to antipsychotic treatment as a warning sign to suspect organicity, as well as the significant improvement in psychiatric impairment when effective and early treatment is established.

Porfiria aguda intermitente com complicações decorrentes do diagnóstico tardio em paciente pediátrico / Acute intermittent porphyria with complications arising from late diagnosis in a pediatric patient

A porfiria é uma doença rara, decorrente da deficiência enzimática associada à biossíntese do grupamento heme. O objetivo deste relato é descrever um caso de crise porfirêmica aguda intermitente em um paciente de 15 anos, que evoluiu rapidamente com tetraplegia e insuficiência renal crônica terminal, além de distúrbios neuropsiquiátricos. Representa uma entidade de difícil diagnóstico devido à inespecificidade dos achados clínicos. À admissão a creatinina era de 6,44 mg/dL e a uréia de 103 mg/dL. Déficit neurológico importante e insuficiência renal crônica são complicações raras, decorrentes do diagnóstico e tratamento tardio. É fundamental que o tratamento seja iniciado imediatamente após o diagnóstico, devido não somente à morbidade a curto-médio prazo, mas também aos possíveis efeitos deletérios permanentes. (AU)

Porphyria is a rare disease, consequence of enzymatic deficiencies associated with heme group biosynthesis. The aim of this report is to describe a case of acute intermittent porphyria crisis in a 15-year-old patient who progressed rapidly with tetraplegia and chronic terminal renal failure, as well as severe neuropsychiatric disorders. It represents an entity of difficult diagnosis due to the lack of specificity of the clinical findings. At admission, creatinine was 6.44 mg / dL and urea was 103 mg / dL. Significant neurological deficit and chronic renal failure are rare complications, arising from late diagnosis and treatment. A greater degree of clinical suspicion is fundamental that treatment be started immediately after diagnosis, due not only to short-term morbidity but also to possible deleterious permanent effects (AU)

Porfiria aguda. Dilema diagnóstico y manifestaciones neuroendocrinas / Acute porphyria. Diagnostic dilemma and neuroendocrine manifestations

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).

Neuropatía periférica como forma de presentación inicial en ataque agudo de porfiria. Reporte de caso clínico / Peripheral neuropathy as initial symptom in porphyria attacks: A case report

Las porfirias constituyen un grupo de ocho enfermedades de baja prevalencia, causadas por defectos enzimáticos en la vía metabólica de la síntesis del grupo hem. Una de sus formas es la porfiria intermitente aguda; afecta a 1,5/100.000 personas año y se presenta con dolor abdominal, taquicardia, parestesias, constipación y vómito. La neuropatía porfírica es en esencia motora, simétrica y suele ser proximal. Se presenta el caso de una paciente de sexo femenino con neuropatía periférica, dolor abdominal y elevación de las transaminasas, en quien se documentó porfiria intermitente aguda. Después de instaurado el manejo, los síntomas se resolvieron...(AU)

Porphyrias are a group of eight low prevalence disorders of heme metabolism, each characterized by a defect in an enzyme required for the synthesis of heme. Acute intermittent porphyria, affecting 1.5 per 100.000 people per year manifesting with abdominal pain, tachycardia, paresthesia, constipation and vomiting, is one type of porphyria. Porphyric neuropathy is fundamentally motor, symmetrical and often has a proximal predilection. A case is presented in a female patient in whom acute intermittent porphyria was documented. Her symptoms included peripheral neuropathy, abdominal pain and elevation of transaminases. Her symptoms resolved after receiving treatment...(AU)

Cirrose hepática secundária à porfiria / Cirrhosis secondary to porphyria

As porfirias são doenças raras que decorrem de deficiência enzimática em uma das oito enzimas que compõem a cadeia de biossíntese do heme e possuem manifestações clínicas variadas. Na maior parte das vezes, são distúrbios hereditários embora existam formas adquiridas. Apresentam ampla interação entre fatores genéticos e fatores ambientais. As manifestações clínicas dependem do tipo de porfirina acumulada, do local onde esta é produzida (fígado ou medula óssea), se acumula da maneira que a mesma é excretada e do mecanismo de toxicidade desta (neurotoxicidade, fotossensibilidade ou ambos). Relatamos um caso de uma paciente do sexo feminino com diagnóstico de cirrose hepática secundária à porfiria que possuía sobrecarga de ferro em exames laboratoriais, sendo descartada a presença de cirrose secundária à hemocromatose.

The porphyrias are rare diseases that result from enzyme deficiency in one of eighteen zymesthat make up the chainof heme biosynthesis and have varied clinical manifestations. In most cases are hereditary disorders, although there are acquired forms. They feature wide interaction between genetican denvironmental factors. Clinical manifestations depend on the accumulated porphyrin, the site where it is produced (liver orbone marrow) and accumulates in the way that it isexcretedand the mechanism of this toxicity (neurotoxicity, photo sensitivity or both). We report a case of a female patient diagnosed with liver cirrhosis secondary to porphyria who had iron overload in laboratory tests being discarded the presence of cirrhosis secondary to hemochromatosis.

La porfiria aguda intermitente y el cirujano: un reto diagnóstico: reporte de un caso y revisión de la literatura / Acute intermittent porphyria and the surgeon: a diagnostic challenge: case report and literature review

La porfiria intermitente aguda es conocida, en el ámbito de la cirugía, como una de las causas de abdomen agudo no quirúrgico. No obstante, lo que no se menciona con frecuencia es la posibilidad de que cualquier procedimiento quirúrgico precipite un episodio agudo en pacientes con predisposición genética. Se presenta un caso florido de porfiria intermitente aguda precipitado por una apendicectomía, el cual complicó el posoperatorio de la paciente hasta el punto de requerir una laparotomía no terapéutica, dado el complejo sintomático de difícil interpretación.

Acute porphyria is an uncommon cause of non surgical acute abdomen. Important is the fact that any surgical intervention could set off an acute attack in particular cases, when the patient has genetical predisposition. We present a case of an acute attack of Intermitent Acute Porphyria triggered by an appendectomy. The patient developed the typical syndrome during the postoperative period, including the abdominal symptoms that imitate an acute abdomen that required a non- therapeutic laparotomy.

Porfiria: uma causa rara de abdômen agudo / Porphyria: a rare cause of acute abdomen

É relatado caso clínico de paciente jovem portadora de porfiria aguda intermitente (PAI), cuja apresentação inicial foi de abdômen agudo. O diagnóstico etiológico tardio, depois de duas intervenções cirúrgicas, foi responsável por significativo aumento da morbidade. O objetivo deste relato é alertar os médicos que atendem em serviços de urgência sobre a importância de se considerar o diagnóstico diferencial do abdômen agudo.

This is a case-report of a young female, adult pacient, with intermitent acute porphyria, whose initial presentation was an acute abdomen. The delayed diagnosis, after two surgical interventions, was responsible of increaded morbity. The objective of this report is to warn doctors that works in emergency centers the importance of the diferential diagnosis in the acute abdomen.

Porfirias: quadro clínico, diagnóstico e tratamento / Porphyrias: clinical presentation, diagnosis and treatment

As porfirias são doenças incomuns e de herança genética na maior parte doscasos. As porfirias são divididas em eritropoiéticas, hepáticas agudas e hepáticas crônicas. Os subtipos de maior relevância clínica são a porfiria cutânea tarda e a porfiria intermitenteaguda. O diagnóstico das porfirias pode ser bastante difícil, dada a sobreposição de quadros clínicos e achados bioquímicos. A precisão do diagnóstico depende da dosagem de porfirinasurinárias e fecais, da análise da atividade enzimática de eritrócitos e, eventualmente, da pesquisa de mutações. O objetivo do presente artigo é realizar revisão literária das porfirias,com ênfase no diagnóstico e tratamento de seus diversos subtipos...

Porphyrias are uncommon diseases that have genetic inheritance in the majorityof the cases. Porphyrias are divided in: erythropoietic porphyria, acute hepatic porphyria and chronic hepatic porphyria. The subtypes with major clinical relevance are porphyria cutaneatarda and acute intermittent porphyria. Diagnosing porphyrias may be quite difficult, as there is significant overlapping between clinical and biochemical findings. The diagnosis depends on the measurement of urinary and fecal porphyrins, enzymatic analysis of erythrocytes and, eventually, analysis of mutations. The main purpose of this article is to make a review of porphyrias, with emphasis on diagnosis and treatment of its several subtypes...

Hemodiálise como terapia alternativa na crise de porfiria intermitente aguda: relato de caso / The use of hemodialysis as alternative therapy for attack of acute intermittent porphyria: case report

JUSTIFICATIVA E OBJETIVOS: A porfiria intermitente aguda (PIA) é uma doença rara e sua crise pode causar lesões irreversíveis, caso não seja tratada precocemente. O tratamento estabelecido se dá com a administração de hematina, substância não disponível no Brasil. O objetivo deste estudo foi relatar um caso em que a hemodiálise foi usada com sucesso como alternativa para tratar uma crise de PIA. RELATO DO CASO: Paciente do sexo masculino, 28 anos, com crise de PIA, importante comprometimento neurológico e alterações autonômicas. Foi tratado com sucesso com sessões diárias de hemodiálise diante da indisponibilidade no Brasil do fármaco de primeira escolha. CONCLUSÃO: A hemodiálise é uma alternativa eficaz para o tratamento das crises de PIA nos países onde a hematina não está disponível. Se realizada precocemente pode evitar sequelas e melhorar a qualidade de vida dos pacientes.

Hemotórax espontáneo: una forma inusual de presentación de la porfiria intermitente aguda / Acute intermittent porphyria presenting as spontaneous hemothorax

Las porfirias son un grupo de alteraciones metabólicas de la síntesis del hem, de carácter hereditario. Son condiciones relativamente raras, de difícil diagnóstico, pero con una respuesta impresionante al tratamiento y con buen pronóstico, si se identifican y tratan a tiempo. La más común de las formas agudas es la porfiria intermitente aguda. Se presenta el caso de un hombre de 23 años que consultó por dolor abdominal y que, concomitantemente presentaba un hemotórax espontáneo de dos litros, presentación inusual nunca antes descrita para la porfiria intermitente aguda. Se incluye una breve revisión de los aspectos más relevantes de la porfiria intermitente aguda, epidemiología, diagnóstico, clínica y manejo, además de una serie de reflexiones sobre cómo sospechar tempranamente el diagnóstico.

The porphyrias are inherited disorders of the heme biosynthetic pathway. They are relatively rare and often misdiagnosed; however, acute episodes can be curtailed by early administration of heme arginate. Acute intermittent porphyria is the commonest of acute forms of porphyria. Here, a case is presented of a 23-year-old male with acute intermittent porphyria who came to the emergency clinic with an unexplained abdominal pain. In addition, he exhibited spontaneous hemothorax (two liters of blood accumulated in the chest) as an unusual manifestation of the disease. The most relevant aspects of acute intermittent porphyria are discussed, along with its epidemiology, diagnosis, clinical presentation and treatment. Complexities and diagnostic requirements in making a diagnosis of porphyria are described.

Estresse oxidativo em porfiria hepâtica experimental disparadapor succinilacetona - urn inibidor da âcido 5-aminolevulinico desidratase / Oxidative stress in experimental hepatic porphyria triggered bysuccinylacetone — an inhibitor of 5-aminoluvulinic acid dehydratase

Para otimizar urn modelo experimental para o estudo do desbalanço redox em porfirias relacionadas ao acúmulo de ácido 5-aminolevulinico-(ALA), via inibição da ALA desidratase-(ALA-D), ratos foram tratados com o éster metílico de succinilacetona-(SAME), um catabólito da tirosina que inibe fortemente a ALA-D, mimetizando o estado metabólico observado nos portadores de porfirias e tirosinemias. Estabeleceram-se modelos de tratamento agudo por 36 e 18 h. No primeiro, os animais receberam 3 injeções de SAME (10, 40 ou 80 mg/kg, grupos All-IV). No segundo, os animais receberam 3 injeções de 40 mg/kg de SAME, ALA ou éster metílico de ALA (grupos BII-IV), ALA:SAME (30:10 mg/kg, grupo BV), ou 10 mg/kg SAME (grupo BVI). Paralelamente, avaliou-se se os sintomas neurológicos característicos das porfirias decorriam de danos oxidativos mitocondriais. Para isso, aplicou-se uma tecnologia óptica para medidas da difusão da depressão cortical que determinou a oxigenação e o estado redox do cit c em mitocôndrias do córtex cerebral de ratos submetidos ao tratamento crônico com ALA (40 mg/kg), SAME (10 e 40 mg/kg) e ALA:SAME (30:10 mg/kg), a cada 48 h, durante 30 dias. Tratamento agudo/36 h: Os níveis de ALA no plasma, fígado, cérebro e urina e o clearance renal do ALA aumentaram nos grupos tratados. A atividade de ALA-D e a coproporfirina urinaria reduziram. A marcação para proteínas carboniladas, ferro e ferritina aumentou no fígado e cérebro dos grupos tratados, especialmente no All. Os níveis de malondialdeído hepática aumentaram no grupo AIV. A razão GSH/GSH+GSSG e a atividade de GPx cerebrais aumentaram nos grupos AIV e AIII, respectivamente. Consistentemente com estes dados indicando um desbalanço oxidativo induzido pelo SAME, alterações mitocondriais e citosólicas ultraestruturais foram reveladas, especialmente no fígado./Tratamento agudo/18 h: Os níveis de ALA plasmáticos aumentaram nos grupos tratados, exceto em BIV. 0 grupo Bll mostrou aumento dos níveis hepáticos...

To optimize an experimental model for studying redox imbalance in porphyrias related to 5-aminolevulinic acid (ALA) accumulation through the inhibition of ALA dehydratase (ALA-D), rats were treated with methyl ester of succinylacetone (SAME), a tyrosine catabolite that strongly inhibits ALA-D, what mimics the metabolic state observed in patients suffering from porphyrias and tyrosinemias. Models of acute treatment were established during 36 and 18 h. In the first model, animals received 3 injections of SAME (10, 40 or 80 mg/kg, groups All-IV). In the second model, animals received 3 injections of 40 mg/kg SAME, ALA or methyl ester of ALA (groups BII-IV), ALA:SAME (30:10 mg/kg, group BV), or 10 mg/kg SAME (group BVI). Concomitantly, we evaluated if the neurologic symptoms characteristics of porphyrias were a consequence of the oxidative mitochondria! impairment. For this, an optical technology for the measurement of cortical spreading depression was applied. This techonology determined the cerebral oxygenation and the redox state of cit c in mitochondria of the cerebral cortex of rats submitted to a chronic treatment with ALA (40 mg/kg), SAME (10 and 40 mg/kg) and ALA:SAME (30:10 mg/kg), alternate days, during 30 days. Acute treatment/36 h: ALA levels in plasma, liver and urine and clearance of renal ALA increased in treated groups. ALA-D activities and urinary coproporphyrin were found to be decreased. Liver and brain proteins carbonyl, iron and ferritin were higher in the liver of treated groups, especially in All. Liver j malondialdehyde levels were higher in group AIV. Cerebral GSH/GSH+GSSG ratio and GPx activities increased in groups AIV and AIII, respectively. Consistently with these data indicating SAME-induced oxidative imbalance, mitochondrial and cytosolic ultrastructural changes were revealed, especially in the liver. Acute treatment/18 h: Plasma ALA levels increased in all treated groups but BIV. Group BII showed increased hepatic ALA levels…

Porfiria aguda en el embarazo: diagnóstico y manejo / Acute porphyria in pregnancy: diagnosis and management

Intermittent acute porphyria during pregnancy is a rare disease. Due to its capacity to simulate an acute abdomen without any apparent cause, it requires an accurate diagnosis and a specific management. This review will present the epidemiology, physiopathology, classification, specific diagnostic criteria and management, focusing on the triggering factors and drugs contraindicated in this diagnosis.

Porfiria aguda intermitente: relato de caso e revisão da literatura / Acute intermittent porphyria: case report and review of the literature

Porfiria aguda intermitente é patologia incomum, com conseqüências potencialmente graves se não reconhecida precocemente. Dentre as possíveis causas de indução de crises de porfiria, a redução da ingestão calórica é descrita na literatura. Relatamos um caso de porfiria aguda intermitente no pós-operatório tardio de gastroplastia indicada para tratamento da obesidade, revisando aspectos do diagnóstico e tratamento da patologia na unidade de terapia intensiva. Paciente feminina, 31 anos, com história de gastroplastia há 3 semanas admitida na unidade de terapia intensiva com rebaixamento do nível de consciência e desconforto respiratório. Evoluiu com agitação psicomotora, confusão mental, dor abdominal e tetraparesia proximal. Na investigação diagnóstica foi encontrado hiponatremia grave (92 mEq/L), hipomagnesemia, hipofosfatemia e hipocalcemia, urina turva, sem hematúria. Aventou-se hipótese de porfiria aguda, realizado dosagem do ácido delta-aminolevulínico e porfobilinogênio na urina de 24h, com elevação de ambos. Iniciado tratamento com dieta rica em carboidratos, sem utilizar hematina ou arginato de heme, devido à dificuldades no fornecimento destas medicações. Evoluiu com melhora clínica gradativa e recuperação completa da força muscular após 8 meses. A porfiria aguda intermitente possui sinais e sintomas comuns a muitas patologias clínicas e neuropsiquiátricas dificultando o diagnóstico, em especial quando estes se manifestam isoladamente. Assim, deve-se incluir a porfiria aguda intermitente no diagnóstico diferencial de distúrbios neurológicos, psiquiátricos e gastroenterológicos em crises, no qual todos os demais exames estejam normais. Atenção deve ser dada a pacientes submetidos à cirurgias, em especial cirurgia bariátrica que, além do estresse cirúrgico, limita substancialmente a ingesta calórica podendo desencadear crises. Não há descrito na literatura, até o momento, nenhum caso de porfiria aguda intermitente no pós-operatório...

Acute intermittent porphyria is an unusual pathology with potentially severe consequences when not early detected. Among the possible causes of porphyric crises decrease of caloric intake has been described. A case of acute intermittent porphyria in the late postoperative period of a bariatric surgery performed for treatment of obesity is reported. A review of the diagnostic aspects and management of this pathology in the intensive care unit follows. A 31 year old woman was admitted in the intensive care unit three weeks after a bariatric surgery, with decreased level of consciousness and respiratory distress. The patient evolved with psychomotor agitation, mental confusion, abdominal pain and proximal tetraparesis. Diagnosis investigation disclosed severe hyponatremia (92mEq/L), hypomagnesemia, hypophosfatemia and hypocalcemia and cloudy urine without hematuria. Acute porphyria was suspected and the urine test detected high delta amino-levulinic acid and porphobilinogen. Treatment consisted of a correction of electrolyte disturbances and high carbohydrate intake. Hematin and heme arginate were not used, due to the difficulty to acquire the medication. After 8 months the patient progressed with full recovery of muscle strength and a clinical improvement. Acute intermittent porphyria has signs and symptoms common to several clinical, neurological, psychiatric and gastroenterological pathologies, which complicate diagnosis. Therefore, acute intermittent porphyria should be included in the differential diagnosis of neurological, psychiatric and gastroenterological alterations when results of all other exams are normal. Attention must be given to patients undergoing surgery mainly bariatric that, in addition to procedure stress, substantially limit the total caloric intake, potentially triggering crises. Review of literature did not disclose any report of acute intermittent porphyria crisis induced by bariatric surgery.

Porfiria y embarazo / Porphyria and pregnancy. Review of 17 women

Hormonal changes, prolonged fasting due to vomiting and some medications used during pregnancy, may cause an acute crisis of porphyria, sometimes unveiling a latent disease. Porphyria may also affect the evolution of pregnancy. Aim: To study the reciprocal influence in the evolution of both pregnancy and porphyria. Material and methods: Retrospective review of medical records of women with porphyria followed by the authors. If additional information was required, an additional visit to the clinic was scheduled. The characteristics of pregnancy, delivery and the newborn were analyzed. Results: Information about 60 pregnancies in 17 women aged 18 to 43 years was gathered. Among women with acute porphyria, one with coproporphyria had four pregnancies, nine with variegate porphyria had a total of 34 pregnancies and two with acute intermittent porphyria had six pregnancies. Five women with porphyria cutánea had a total of 16 pregnancies. Influence of porphyria in pregnancy: Compared to the general population, no differences were observed in birth weight of newborns, frequency of gestational hypertension, term or preterm deliveries of live newbornss, spontaneous abortions nor in tubal pregnancies; there was a high frequency of hyperemesis gravidarum. Influence of pregnancy in porphyria: 5 of the 12 patients with acute porphyria, had an acute porphyria crisis, 3 during the puerperal period and 2 during pregnancy (42 percent of women, 11 percent of pregnancies). All these crisis were associated to the administration of medications. All patients survived. Two of these women had six ulterior pregnancies without complications. Conclusions: Women with porphyria that become pregnant have a higher frequency of hyperemesis gravidarum. Crises among women with acute porphyrias, were always associated with the use of potentially dangerous medications.