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Deficiência múltipla das Acil-CoA desidrogenases : considerações a propósito de 4 casos clínicos
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Advisor(s)
Abstract(s)
A Deficiência Múltipla das Acil-CoA Desidrogenases (MADD), também designada Acidúria Glutárica Tipo II, é uma doença hereditária do metabolismo, resultante de um défice enzimático que afeta sobretudo a ß-oxidação mitocondrial dos ácidos gordos.
É causada por mutações que levam à deficiência da flavoproteína transportadora de eletrões (ETF) ou da sua desidrogenase (ETFDH). A transmissão é autossómica recessiva e os genes envolvidos são o ETFDH, o ETFA ou o ETFB.
Ocorre acumulação de metabolitos tóxicos e falência da produção de energia a partir de ácidos gordos durante períodos de jejum, sobretudo a nível do músculo esquelético e do coração. O fenótipo clínico é heterogéneo e pode classificar-se em 3 grupos consoante o início e gravidade das manifestações. A apresentação pode incluir hipotonia, fraqueza muscular e rabdomiólise, ou apenas episódios de descompensação metabólica aguda. As complicações da doença incluem a esteatose hepática, cardiomiopatia, arritmias cardíacas, falência multissistémica e morte súbita.
A MADD é uma das doenças incluídas no programa de rastreio metabólico neonatal alargado português, podendo ser diagnosticada precocemente.
Este artigo relata quatro casos clínicos da Deficiência Múltipla das Acil-CoA Desidrogenases, acompanhado de uma pequena revisão teórica e descrição dos diversos cursos clínicos, tratamento e seguimento aconselhado.
São ainda discutidos tópicos de relevo, como o aconselhamento familiar que deve ser realizado nestes casos, a incerteza do prognóstico e curso da doença e a ocorrência de morte súbita, salientando-se a importância de investir no estudo mais aprofundado sobre a doença.
Multiple Acyl-CoA Dehydrogenase Deficiency (MADD), also called Glutaric Aciduria Type II, is an inherited metabolic disease, resulting from an enzyme deficit that affects mainly the mitochondrial ß-oxidation of fatty acids. MADD is caused by mutations in electron-transfer flavoprotein (ETF), or electron-transfer flavoprotein dehydrogenase (ETFDH). It is an autosomal recessive disease caused by mutations in the ETFDH, ETFA or ETFB genes. There is an accumulation of toxic metabolites and a lack of energy production from fats during periods of fasting, mostly at the level of skeletal muscle and heart. The clinical phenomenon is heterogeneous and can be classified into 3 groups according to the onset and severity of the manifestations. The symptoms may consist of hypotonia, muscle weakness and rhabdomyolysis or episodes of acute metabolic decompensation. Among the several complications are included hepatic steatosis, cardiomyopathy, cardiac arrhythmias, multisystemic failure and sudden death. MADD is one of the diseases comprised in the Portuguese Expanded Newborn Screening, enabling its early diagnosis. This article reports four clinical cases of Multiple Deficiency of Acyl-CoA Dehydrogenases, accompanied by a short theoretical review and description of the different clinical courses, treatment and recommended follow-up. Other relevant topics are also discussed, such as the significance of family counselling in these cases, the uncertainty of the prognosis and course of the disease, and the occurrence of sudden death, while stressing the importance of investment in a more in-depth study of the disease.
Multiple Acyl-CoA Dehydrogenase Deficiency (MADD), also called Glutaric Aciduria Type II, is an inherited metabolic disease, resulting from an enzyme deficit that affects mainly the mitochondrial ß-oxidation of fatty acids. MADD is caused by mutations in electron-transfer flavoprotein (ETF), or electron-transfer flavoprotein dehydrogenase (ETFDH). It is an autosomal recessive disease caused by mutations in the ETFDH, ETFA or ETFB genes. There is an accumulation of toxic metabolites and a lack of energy production from fats during periods of fasting, mostly at the level of skeletal muscle and heart. The clinical phenomenon is heterogeneous and can be classified into 3 groups according to the onset and severity of the manifestations. The symptoms may consist of hypotonia, muscle weakness and rhabdomyolysis or episodes of acute metabolic decompensation. Among the several complications are included hepatic steatosis, cardiomyopathy, cardiac arrhythmias, multisystemic failure and sudden death. MADD is one of the diseases comprised in the Portuguese Expanded Newborn Screening, enabling its early diagnosis. This article reports four clinical cases of Multiple Deficiency of Acyl-CoA Dehydrogenases, accompanied by a short theoretical review and description of the different clinical courses, treatment and recommended follow-up. Other relevant topics are also discussed, such as the significance of family counselling in these cases, the uncertainty of the prognosis and course of the disease, and the occurrence of sudden death, while stressing the importance of investment in a more in-depth study of the disease.
Description
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2020
Keywords
Deficiência múltipla das Acil-CoA desidrogenases ß-oxidação dos ácidos gordos Descompensação metabólica Arritmias cardíacas Morte súbita Pediatria