Baseline clinical characteristics and disease burden of patients with aromatic L-amino acid decarboxylase deficiency (AADCd) enrolled in the AADCAware registry

Bruria Ben Zeev ¹ Agathe Roubertie ² Phillip L Pearl ³ Fatih Ezgu ⁴ Paul Lupo ⁵ Emelline Liu ⁵ Shelley Johnson ⁵ J Rafael Sierra ⁵ Roberto Giugliani ⁶ Roberta Battini ^7,8 Lucinda Carr ⁹

¹Sheba Medical Center, Israel
²Centre Hospitalier Universitaire de Montpellier, France
³Boston Children’s Hospital, USA
⁴Gazi University Faculty of Medicine, Turkiye
⁵PTC Therapeutics, USA
⁶UFRGS, HCPA, INAGEMP, Dasa Genomica, and Casa dos Raros, Brazil
⁷Department of Clinical and Experimental Medicine, University of Pisa, Italy
⁸Developmental Neuroscience Department, IRCCS Stella Maris Foundation, Italy
⁹Great Ormond Street Hospital, UK

Background: Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare, often life-limiting genetic neurotransmitter disorder. AADCAware is a patient registry designed to describe the natural history of AADCd in patients receiving standard of care and assess the long-term safety and effectiveness of eladocagene exuparvovec on motor function. Baseline demographics and disease characteristics of untreated patients up to March 2023, are described.

Methods: AADCAware is an international, multicenter, longitudinal, real-world, observational registry of patients with AADCd. Participants are followed up annually for ≥5 years. Motor development status was assessed using the Peabody Developmental Motor Scale-2 (PDMS-2).

Results: At enrolment, the study population (N=45) had a median (min, max) age of 3 (1, 41) years and were predominately White (29 [65.9%]). Median (min, max) ages at onset of first symptoms was 3 (0, 12) months. The most commonly reported central nervous system (CNS) signs and symptoms at enrolment were delayed motor and speech development (both 84.4%), delayed cognitive development (82.2%), hypotonia (77.8%), poor head control (68.9%), oculogyric episodes (57.8%), and hypokinesia/bradykinesia (48.9%). Common autonomic signs/symptoms included excessive sweating (46.7%), excessive drooling (40.0%), nasal congestion (31.1%), ptosis (28.9%), and temperature instability (24.4%). Patients also reported feeding/swallowing (46.7%), gastrointestinal (42.2%) and cardiovascular problems (13.3%). Of 31 patients with data, 24 (77.4%) had not developed full head control or were unable to sit unassisted and 25 (80.7%) were unable to stand or walk with support. Eleven patients (24.4%) discontinued the registry; 32 patients (71.1%) remain in the study; 2 patients (4.4%) died.

Conclusion: These results show that patients with AADC deficiency present with a wide spectrum of CNS and autonomic signs and symptoms. AADCAware will help to gain a better understanding of AADCd.