PTC symposium| AADC deficiency: diagnosis and management

Authors: Prof. Fatih Ezgü, Prof. Karl Kiening, Mr Richard Poulin and Mrs Judy Poulin
Arising from pathogenic variants in the DDC gene, AADC deficiency is a rare neurometabolic disorder that leads to severe combined deficiency of dopamine, serotonin, adrenaline and noradrenaline [1,2].  Absence of these neurotransmitters leads to delayed motor development, movement disorders, autonomic dysfunction and mood disturbances [1–3]. When these clinical manifestations are observed, it is recommended to test for AADC deficiency [2]. A diagnosis of AADC deficiency requires positive results in at least two of the three core tests – single gene or genetic panel testing to assess for pathogenic variants in the DDC gene, a plasma sample to evaluate AADC enzyme activity and a CSF neurotransmitter metabolite panel to detect alterations in metabolite levels [1,2]. Practical considerations for diagnosis and management will be explored in this symposium through the use of real-world case studies.

While management options for patients have been limited to symptomatic treatment [1,2] recent advances in the therapeutic landscape have employed gene therapy to address the underlying AADC deficiency [4–6]. The rationale behind intraputaminal AADC gene therapy, as well as long-term safety and efficacy clinical data, and stereotactic procedure to administer the treatment will be discussed.

From the perspective of caregivers of a child with AADC deficiency, the diagnostic journey has many challenges. Disease awareness and perseverance are key to ensuring appropriate management and care is provided [1]. We will hear from parents of a child with AADC deficiency; they will discuss the impact the condition has had on both themselves and their child and how gene therapy has affected their quality of life. The symposium will conclude with a live panel discussion to further discuss the key themes and concepts presented throughout the sessions.

References

1. Wassenberg T, et al. Orphanet J Rare Dis. 2017;12(1):12.
2. Himmelreich N, et al. Mol Genet Metab. 2019;127(1):12–22.
3. Chien YH, et al. Lancet Child Adolesc Health. 2017;1(4):265–273.
4. Pearson TS, et al. Nature Commun. 2021;12(1):4251.
5. Tai C-H, et al. Mol Ther. 2022;30(2):509–518.
6. Hwu PW-L, et al. EMBO Mol Med. 2021;13(9):e14712.

PTC symposium - AADC deficiency: diagnosis and   management
NEW   PARADIGM IN AADC DEFICIENCY: DIAGNOSIS AND MANAGEMENT

13:00–13:03    Welcome, introductions and objectives
Prof. Fatih Ezgü (Chair) Department of Paediatric Genetic and   Metabolic Disorders, Gazi University, Ankara, Türkiye

13:03–13:18    An introduction to AADC deficiency: Practical considerations   of diagnosis and management from real-world experience
Prof. Fatih Ezgü, Department of Paediatric Genetic and   Metabolic Disorders, Gazi University, Ankara, Türkiye

13:18–13:33    Intraputaminal gene therapy for AADC deficiency: An overview   of clinical data from trials of eladocagene exuparvovec    Prof. Karl Kiening, Department of Neurosurgery, University   Hospital Heidelberg, Heidelberg, Germany

13:33–13:43    A caregiver’s perspective on the AADC deficiency diagnostic   journey and insights into quality of life following gene therapy    Mr Richard Poulin and Mrs Judy Poulin, Carers of daughter,   Rylae-Ann, a patient with AADC deficiency

13:43–13:58    Panel discussion
All faculty

13:58–14:00    Summary and close
Prof. Fatih Ezgü (Chair) Department of Paediatric Genetic and   Metabolic Disorders, Gazi University, Ankara, Türkiye