(P-285) Global Symptom Improvement for Patients with Aromatic L-amino Acid Decarboxylase Deficiency Using Individual Participant Data

Background: AADC-d is a rare disease with a wide range of symptoms including movement disorders, developmental delays, and autonomic symptoms from birth. There is limited available information on the relationship between different symptoms, particularly measures of cognitive development and motor development.

Objectives: This work uses available data on patients to explore global symptom improvement.

Methods: Study

Design: Patient level data from three single-armed trials exploring the impact of therapy on patients with AADC-d was used to estimate the relationship between motor and cognitive development.
Study Participants & Setting: Data were available for 28 patients across the three trials with follow-up times from 12 to 108 months. These patients were 2-9 years old and had severe AADC-d with no attainment of motor-milestones at baseline.
Materials/

Methods: Patient level data from the trials were analysed to explore the impact of therapy on absolute cognitive and motor developmental scores (Bayley III and PDMS-2) and the attainment of motor milestones. Pearson’s correlation coefficients were estimated between Bayley III, PDMS-2 and Motor milestone achievement. Additionally, scatter plots were drawn for visual interpretation of the relationships.

Results: Initial data analyses indicated a high level of association between cognitive development and motor milestone achievement among patients in the trials. Correlation between motor milestones and cognition was estimated to be 0.75, while the correlation between PDMS-2 scores and cognition was estimated to be 0.94. Heterogeneity was observed in attainment of motor milestones across the population. Similarly, patients’ trajectories over time are subject to a large degree of variance.

Conclusions: This trial data analysis provides evidence to fill a gap in the literature for AADC-d patients’ outcomes. Even with a modest amount of patient data, it has been possible to find a strong relationship between cognitive and motor development for patients with AADC-d. The results of this work will be used to help inform a cost-effectiveness model to support reimbursement of a therapy for AADC-d patients.