P.037 Refractory status dystonicus and hypotension after cardiac arrest in a child with AADC deficiency post gene therapy: a case report

Abstract

Background: Aromatic l-amino acid decarboxylase (AADC) deficiency is a metabolic disorder that causes deficient serotonin, dopamine, and catecholamine synthesis. How children respond to neurological insult post intracranial gene therapy remains underreported. We present a 10 year old girl with profound neurological injury after a brief in-hospital cardiac arrest, secondary to viral infection-induced respiratory failure, 4 years after gene therapy. Methods: Patient’s chart review included brain imaging, clinical notes, laboratory results, and treatment. Results: MRI showed symmetric abnormalities in the basal ganglia, thalami, cortex, and cerebellar hemispheres. CSF analysis showed homovanillic acid 27 nmol/L (reference range 167-563) and 5-hydroxyindoleacetic acid 7 nmol/L (reference range 67-189). She developed generalized dystonia and oculogyric crises which were not seen since before gene therapy. There was poor catecholamine production causing refractory hypotension. She required a one-month stay in ICU for hypotension and status dystonicus. Dystonia was controlled with high doses of 6 agents. Conclusions: We describe a patient with AADC deficiency post gene therapy who experienced disproportionately severe neurological injury and decreased AADC activity after hypoxic neurological insult. There may be unique considerations of dopaminergic neuron integrity, AADC gene promoter sensitivity, and cerebrovascular autoregulation in children with AADC deficiency post gene therapy.