RESUMO
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RESUMO
BACKGROUND: Mitochondrial and neurogenetic diseases can present diagnostic challenges. We investigated if near infrared spectroscopy with the vascular occlusion test is able to differentiate between children with mitochondrial disease and children with neurogenetic disease or healthy controls. METHODS: Prospective observational study conducted in a tertiary children's hospital. RESULTS: Forty-three children with mitochondrial disease (including both genetically confirmed primary mitochondrial disease and cases with biochemical evidence of mitochondrial dysfunction), 19 children with non-mitochondrial neurogenetic disease and 13 healthy controls were recruited. The delta tissue oxygen index (ΔTOI) values showed greater variability amongst children with mitochondrial disease and neurogenetic disease than healthy controls despite the median ΔTOI being similar (median 14.1 and 18.8, t-test, p = 0.16). A low ΔTOI identifies cases with a higher probability of mitochondrial disease or neurogenetic disease compared to healthy controls (positive likelihood ratio: 3.67; 95%CI:1.01-13). A high ΔTOI with the near infrared spectroscopy with vascular occlusion test identifies cases with a lower probability of having a disease (negative likelihood ratio: 0.51; 95%CI:0.36-0.74). CONCLUSION: Near infrared spectroscopy with vascular occlusion test might be able to discriminate children with mitochondrial disease and neurogenetic disease from healthy controls.
Assuntos
Biomarcadores/análise , Predisposição Genética para Doença , Doenças Mitocondriais/diagnóstico , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/genética , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Doenças Vasculares/fisiopatologia , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Doenças Mitocondriais/diagnóstico por imagem , Doenças Mitocondriais/metabolismo , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/metabolismo , Consumo de Oxigênio , Estudos Prospectivos , Doenças Vasculares/diagnóstico por imagemRESUMO
PurposeMutations in POLG, the most common single-gene cause of inherited mitochondrial disease, are diagnostically challenging owing to clinical heterogeneity and overlap between syndromes. We aimed to improve the clinical recognition of POLG-related disorders in the pediatric population.MethodsWe performed a multinational, phenotype: genotype study using patients from three centers, two Norwegian and one from the United Kingdom. Patients with age at onset <12 years and confirmed pathogenic biallelic POLG mutations were considered eligible.ResultsA total of 27 patients were identified with a median age at onset of 11 months (range 0.6-80.4). The majority presented with global developmental delay (n=24/24, 100%), hypotonia (n=22/23, 96%) and faltering growth (n=24/27, 89%). Epilepsy was common, but notably absent in patients with the myocerebrohepatopathy spectrum phenotype. We identified two novel POLG gene mutations.ConclusionOur data suggest that POLG-related disease should be suspected in any child presenting with diffuse neurological symptoms. Full POLG sequencing is recommended since targeted screening may miss mutations. Finally, we simplify the classification of POLG-related disease in children using epilepsy as the crucial defining element; we show that Alpers and myocerebrohepatopathy spectrum follow different outcomes and that they manifest different degrees of respiratory chain dysfunction.