A group of leading experts in pediatric neurology and movement disorders attended a virtual roundtable to discuss diagnostic, symptomatic, and research aspects of aromatic L-amino acid decarboxylase (AADC) deficiency.

AADC deficiency is characterized by a defect in the dopa decarboxylase or DDC gene; this dysfunction leads to reduced production of the critical neurotransmitters dopamine, norepinephrine, epinephrine, and melatonin. As a result, patients with AADC deficiency can suffer deficits in vital motor function.

The symptoms of this very rare genetic disorder usually appear before children reach one year of age. Patients with severe symptoms rarely survive beyond age 10. Although patients with moderate symptoms can live into adulthood, those afflicted with AADC deficiency often experience developmental disability and can require lifelong care. The participants included:

Philip L. Pearl, MD
Director, Epilepsy and Clinical Neurophysiology, Boston Children’s Hospital
William G. Lennox Chair and Professor of Neurology, Harvard Medical School
Boston, MA

Warren A. Marks, MD
Medical Director, Movement Disorders
Cook Children’s Jane and John Justin Neurosciences Center
Fort Worth, TX

Paul Wuh-Liang Hwu, MD, PhD
Professor, Department of Pediatrics and Medical Genetics
National Taiwan University Hospital
Tapei, Taiwan

Irina A. Anselm, MD
Director of the Mitochondrial Program and Co-Director of the Neurometabolic Program, Boston Children’s Hospital
Assistant Professor of Neurology, Harvard Medical School
Boston, MA

Jennifer O’Malley, MD, PhD
Clinical Assistant Professor, Neurology & Neurological Sciences, Stanford Medicine
Pediatric Neurologist, Stanford Children’s Health
Stanford, CA

Moderated by Dr. Pearl, the roundtable participants described the first recognized case of AADC deficiency, and the fact that the prevalence and incidence of the condition is not yet clear. One problem is that the presentation of infants with AADC deficiency is not very specific, and a large number of patients are probably not yet diagnosed, said Dr. O’Malley. Unexplained hypotonia is a useful sign, she explained, which clinicians can use to go down the path to diagnosis. Dr. Marks commented that when children present with movement disorders at his center, he has a very low threshold to begin genetic testing for AADC deficiency, which will rapidly eliminate or confirm the diagnosis. Dr. Hwu emphasized that clinical recognition is the first step: Once you make one diagnosis, it isn’t too difficult to identify the second patient.

Symptomatic treatment can be useful, particularly in patients with milder forms of AADC deficiency, said Dr. Anselm. For example, similar to Parkinsonism, dopamine agonists can have positive results, but dyskinesias are problematic.

Gene therapy holds promise, according to Dr. Hwu, but he cautioned that even if successful, a good deal of movement training and patience will be required to gain movement control.

Drs. O’Malley and Anselm believe that collaboration and education among the different disciplines (e.g., child neurologists and physiatrists) is key to improving recognition of AADC deficiency and gaining early treatment.