Clinical Presentation and Follow-Up of Two AADC Deficiency Cases in Brazil Before Gene Therapy

BACKGROUND

L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disorder that leads to defective synthesis of monoamine transmitters. Early infancy symptoms are wide-ranging, mainly severe arrested motor development

CASE REPORT

Two AADC cases diagnosed before 2 years of age and their follow-up. Case 1: male with no perinatal or family history presented with hypotonia, dysphagia, oculogyric crisis and dyskinetic movements. He was treated for refractory epilepsy. Genetic epilepsy testing identified two compound heterozygous DDC gene pathogenic variants p.Gln190Profs*13 and p.Arg347Gln. The diagnosis was confirmed with low plasmatic enzyme activity (0.08 nmol/L/min, -8.87−85.21). He did not achieve motor milestones, was aware of his environment, and responded to stimuli and his parents. He was treated with Pyridoxine and Bromocriptine with no improvement. Subsequently, he was approved for treatment with gene therapy but died at 2 years of age in April 2023 from dystonic status and severe autonomic dysfunction treating pneumonia. Case 2: female with no perinatal or family history who had hypotonia and few spontaneous movements in her early months of life. At 4 months of age during hospitalization, she presented with developmental delay, hypotonia, dysphagia, couldn’t hold her head and had few eye movements. Negative extensive research for hypotonic infant syndrome: MRI, EEG and biochemical analysis. Two compound heterozygous pathogenic variants p.Arg347Gln and p.Trp121Arg were identified in the DDC gene. At this point, oculogyric crises and dystonic movements started, as well as low enzyme activity (0.84 pmol/min/mL, -36−129). After diagnosis, she was treated with Pyridoxin and Bromocriptine according to the 2017 guideline but with no response. She improved with Selegiline, mainly oculogyric crises and dystonia and is currently awaiting approval for gene therapy.

DISCUSSION

AADC deficiency is a known severe metabolic disease that is presented as hypotonia, dyskinesia and oculogyric crisis. Early diagnosis, although challenging, could change the patient outcome since it is now treatable with gene therapy.