Dados do Trabalho

Título

INFANTILE SPASMS RELATED TO POLG MUTATION: A CASE REPORT

Apresentação do caso

CASE PRESENTATION: A ten-month-old female infant, previously healthy, presented with fever, irritability and within a few days she developed focal seizures, orofacial dyskinesia and right hemiparesis. MRI brain, cerebrospinal fluid analysis and antibody panel for autoimmune encephalitis did not show abnormalities. After ruling out an infectious condition, she was treated empirically with methylprednisolone, IVIG and cyclophosphamide, which led to limited results. Metabolic analysis profile were normal. The child was initially treated with Valproic acid, Oxcarbazepine and Nitrazepam without improvement. During hospitalization, she developed infantile spasms. Serial EEGs showed hypsarrhythmia and, later on, multifocal activity. She received long courses of corticosteroids plus vigabatrine with a slight improvement. At discharge, the spasms persisted even on polytherapy with vigabatrin, cannabidiol, clobazam and levetiracetam. At outpatient follow-up, a genome was performed. Two pathogenic mutations in heterozygosity were identified in the POLG gene (c.1760C>T and c.752C>T) and a variant of uncertain meaning in the MECP2 gene. Considering the possibility of POLG-related mitochondrial epilepsy with compound heterozygosity, coenzyme Q10, folinic acid and ketogenic diet were initiated, with a remarkable improvement in seizure control. Seizures dropped from 60 to around 30 events per day. Besides, the patient has been presenting a recovery in motor and social functions.

Discussão

DISCUSSION: POLG1 is an enzyme responsible for the accuracy in replicating mitochondrial DNA. The clinical spectrum of POLG1 gene mutations is comprehensive, ranging from epilepsy and few neurological signs to severe neurodegenerative disorders. Epilepsy is one of the most common manifestations. Patients usually have epileptiform abnormalities in occipital regions and increased T2 signal in thalamic regions, which was not seen in our case. Regarding treatment, until now, there are few reports of success in seizure control, and, in general, the outcome is poor. The beneficial effect of the ketogenic diet has been previously reported, as seen in this case report.

Comentários finais

FINAL COMMENTS: We conclude that POLG-related mitochondrial epilepsy, although rare, is one of the possible causes of infantile spasms. Even with partial control of seizures, in this case, a ketogenic diet must be considered an alternative of treatment. The prognosis is poor, with survival inversely related to the age at onset of seizures.