1 - Child Neurology Unit, Pediatrics Department, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisboa
2 - Pediatric Cardiology Department, Hospital Santa Marta, Centro Hospitalar Universitário Lisboa Central, Lisboa
3 - Genetics Department, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisboa 4 Neonatal Intensive Care Unit, Pediatrics Department, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisboa
- Reunião internacional: 14th European Paediatric Neurology Society Congress
Objective: Neurological differential diagnosis of neonatal respiratory failure associated with hypotonia is broad.
Methods: Case report
Results: A male term neonate presented respiratory insufficiency shortly after birth, requiring invasive ventilation. He had no dysmorphisms, contractures or fasciculations, had normal DTRs but variable axial hypotonia and alternating periods of active movements with global inactivity. Eyes were mostly closed for the first weeks but no ophtalmoparesis, ptosis or facial palsy was observed when open. He was thoroughly studied by ENT and Pneumology. Neonatal cardiosonography revealed slight interventricular sept hypertrophy. CK and thyroid hormones were normal, AChR, MusK and LRP4 autoantibodies were negative. Brain and cervical spine MRI, motor NCS and EMG were normal (SFEMG and repetitive stimulation were not performed). Extubation was not successful due to rapidly progressive respiratory distress and severe lactic acidosis. Considering a congenital myasthenic syndrome, SC neostigmine was started, with clear improvement of global muscle activity. Severe cholinergic effects occurred, requiring advanced resuscitation and atropine. Switching to oral piridostigmine and dosage reduction was successful with progressively less severe adverse effects. Oral salbutamol was added and transition to non-invasive ventilation was possible. After two weeks of stability, acute decompensation occurred, requiring invasive ventilation and hypertrophic cardiomyopathy with large pericardic effusion was detected. After drainage, non-invasive ventilation was resumed but lactic acidosis became systematically present. On day 60, exome sequencing identified two apparently compound heterozygous variants in VARS2 gene.
Conclusions: This patient with VARS2-related disorder had a definite response to acetilcholinesterase inhibitors and salbutamol. We suggest this mitochondrial encephalocardiomyopathy should be included in the differential diagnosis of neonatal respiratory failure with variable muscle tone.
Palavras Chave: respiratory failure, neonate, myasthenia, VARS2 gene