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Síndrome de Aicardi-Goutières : um desafio neuroimunológico
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A Síndrome de Aicardi-Goutières (SAG) designa uma encefalopatia geneticamente determinada, mais frequentemente segundo um padrão de herança autossómico recessivo. A apresentação clínica clássica tem instalação progressiva e ocorre no primeiro ano de vida. Caracteriza-se por microcefalia adquirida, calcificações simétricas nos gânglios da base, leucodistrofia, linfocitose com pleiocitose crónica e níveis aumentados de interferão α (IFN-α) no líquor pelo que a imagiologia e o doseamento de interferão constituem os principais auxiliares diagnósticos. Estes achados traduzem-se clinicamente por atraso ou regressão no desenvolvimento psicomotor, espasticidade e sinais extra-piramidais.
O caso clínico descreve um lactente do sexo masculino que aos 2 meses se apresenta com irritabilidade e alterações dos movimentos oculares de instalação aguda. A tomografia axial computorizada revelou múltiplas calcificações cerebrais e atrofia cerebral. Da investigação realizada destacam-se estudos infecioso e metabólico sem alterações, doseamento de IFN-α no líquido cefalorraquidiano (LCR) superior a 100 UI/mL (valor de referência inferior a 2 UI/mL) e estudo genético diagnóstico de SAG, com duas mutações no gene TREX1. A evolução mostrou-se desfavorável e as sequelas permanentes, com tetraparesia espástica, epilepsia e comorbidades associadas.
A doença evidencia-se como um raro, mas importante diagnóstico diferencial na presença de encefalopatia em idade pediátrica, ao mimetizar uma infeção congénita e como paradigma de um grupo heterogéneo de doenças que partilham mecanismos fisiopatológicos.
Até à data, a progressão da doença é inevitável. O diagnóstico atempado, no qual se destaca o reconhecimento de padrões radiológicos, pode permitir uma intervenção precoce e possibilitar uma estratégia que acompanhe o emergir de novas abordagens terapêuticas.
Aicardi-Goutières Syndrome (AGS) refers to a genetic encephalopathy most often with a recessive autosomal pattern of inheritance. The classical clinical presentation has a progressive onset and occurs within the first year of life. It is characterized by acquired microcephaly, symmetric basal ganglia calcifications, leukodystrophy, lymphocytosis with chronic cerebrospinal fluid (CSF) pleocytosis and raised interferon-alpha (IFN-α) in CSF. Therefore, image scans and interferon assays are the main diagnostic methods. These findings clinically translate to a delay or regression in normal psychomotor development, spasticity and extrapyramidal symptoms. The case report describes a two-month-old male infant that presents with irritability and sudden ocular motor abnormalities. Computerized tomography (CT) scans revealed multiple intracranial calcifications and cerebral atrophy. Investigations found no changes in infectious and metabolic markers, but IFN-α in CSF was above 100 UI/mL (reference value of less than 2 IU/mL) and genetic tests confirmed the diagnosis of AGS revealing two TREX1 mutations. The outcome was unfavorable with permanent sequelae, namely spastic tetraparesis, epilepsy and several comorbidities. The condition stands out as a rare but important differential diagnosis in the presence of childhood encephalopathy by mimicking congenital infections and as paradigm of a heterogeneous group of diseases which share pathophysiological mechanisms. To date, disease progression is inevitable. An early diagnosis in which recognizing neuroradiologic patterns is crucial may allow for a prompt intervention and enable the use of emerging therapeutic approaches.
Aicardi-Goutières Syndrome (AGS) refers to a genetic encephalopathy most often with a recessive autosomal pattern of inheritance. The classical clinical presentation has a progressive onset and occurs within the first year of life. It is characterized by acquired microcephaly, symmetric basal ganglia calcifications, leukodystrophy, lymphocytosis with chronic cerebrospinal fluid (CSF) pleocytosis and raised interferon-alpha (IFN-α) in CSF. Therefore, image scans and interferon assays are the main diagnostic methods. These findings clinically translate to a delay or regression in normal psychomotor development, spasticity and extrapyramidal symptoms. The case report describes a two-month-old male infant that presents with irritability and sudden ocular motor abnormalities. Computerized tomography (CT) scans revealed multiple intracranial calcifications and cerebral atrophy. Investigations found no changes in infectious and metabolic markers, but IFN-α in CSF was above 100 UI/mL (reference value of less than 2 IU/mL) and genetic tests confirmed the diagnosis of AGS revealing two TREX1 mutations. The outcome was unfavorable with permanent sequelae, namely spastic tetraparesis, epilepsy and several comorbidities. The condition stands out as a rare but important differential diagnosis in the presence of childhood encephalopathy by mimicking congenital infections and as paradigm of a heterogeneous group of diseases which share pathophysiological mechanisms. To date, disease progression is inevitable. An early diagnosis in which recognizing neuroradiologic patterns is crucial may allow for a prompt intervention and enable the use of emerging therapeutic approaches.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2018
Palavras-chave
Síndrome de Aicardi-Goutières Encefalopatia Pediatria