RESUMO
Mitochondrial disorders are often difficult to diagnose because of diverse clinical phenotypes. FGF-21 and GDF-15 are metabolic hormones and promising biomarkers for the diagnosis of these disorders. This study has systematically evaluated serum FGF-21 and GDF-15 levels by ELISA in a well-defined cohort of patients with definite mitochondrial disorders (n = 30), neuromuscular disease controls (n = 36) and healthy controls (n = 36) and aimed to ascertain their utility in the diagnosis of mitochondrial disorders. Both serum FGF-21 and GDF-15 were significantly elevated in patients with mitochondrial disorders, especially in those with muscle involvement. The levels were higher in patients with mitochondrial deletions (both single and multiple) and translation disorders compared to respiratory chain subunit or assembly factor defects.
Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Marcadores Genéticos , Fator 15 de Diferenciação de Crescimento/metabolismo , Doenças Mitocondriais/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Fatores de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Fator 15 de Diferenciação de Crescimento/genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Reports on magnetic resonance imaging findings in patients with short chain acyl -Coenzyme A dehydrogenase (SCAD) deficiency, an autosomal recessive disorder caused by mutations in the acyl-Coenzyme A dehydrogenase (ACADS), are limited. Many asymptomatic carriers of ACAD variants have also been described necessitating careful evaluation of clinical and biochemical findings for an accurate diagnosis. Here we report a an infant with short chain acyl -Coenzyme A dehydrogenase (SCAD) deficiency diagnosed based on the characteristic biochemical findings and confirmed by genetic testing. He presented with refractory seizures and neuro regression at 4 months of age. His metabolic work up revealed elevated butyryl carnitine in plasma and ethyl malonic acid in urine. Magnetic resonance imaging of the brain showed cortical and basal ganglia signal changes with cortical swelling. Serial scans showed progression of the lesions resulting in cystic leukomalacia with brain atrophy. Exome sequencing revealed a novel homozygous nonsense variation, c.1146C > G (p.Y382Ter) in exon ten of ACADS which was further validated by Sanger sequencing. Both parents were heterozygous carriers. Follow up at 15 months showed gross psychomotor retardation and refractory seizures despite being on optimal doses of anti-epileptic medications, carnitine and multivitamin supplementation. This report expands the phenotypic and genotypic spectrum of SCAD deficiency.
