Infectious stress triggers a POLG-related mitochondrial disease.
Neurogenetics
; 21(1): 19-27, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31655921
ABSTRACT
A 3-year-old girl presented with severe epilepsy in the context of Borrelia infection. After ceftriaxone/lidocaine administration, she showed secondarily generalized focal crises that led to neurological and motor sequelae. Genetic studies identified in the patient two heterozygous POLG mutations (c.2591A>G; p.Asn864Ser and c.3649G>C; p.Ala1217Pro). Through analysis of POLG activity in cultured fibroblasts, we confirmed that the mutations altered the mtDNA turnover. Moreover, patient fibroblasts were more sensitive than controls in the presence of a mitochondrial replication-affecting drug, the antiretroviral azidothymidine. To test if ceftriaxone treatment could worsen the deleterious effect of the patient mutations, toxicity assays were performed. Cell toxicity, without direct effect on mitochondrial respiratory function, was detected at different antibiotic concentrations. The clinical outcome, together with the different in vitro sensitivity to ceftriaxone among patient and control cells, suggested that the mitochondrial disease symptoms were hastened by the infection and were possibly worsened by the pharmacological treatment. This study underscores the benefit of early genetic diagnosis of the patients with mitochondrial diseases, since they may be a target group of patients especially vulnerable to environmental factors.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Infecções por Borrelia
/
Doenças Mitocondriais
/
Epilepsia
/
DNA Polimerase gama
/
Mutação
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Child, preschool
/
Female
/
Humans
Idioma:
En
Revista:
Neurogenetics
Assunto da revista:
GENETICA
/
NEUROLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Espanha