As part of the roundtable moderated by Philip Pearl, MD, of Boston Children’s Hospital and Harvard Medical School, the attendees of this virtual discussion focused on key diagnostic aspects of aromatic L-amino acid decarboxylase (AADC) deficiency. The entire AADC deficiency Panel Discussion can be viewed here.
Dr. Hwu emphasized that clinical recognition of some of the specific physical manifestations is the first step to diagnose this very rare condition. In the past few years, a testing panel has been developed for AADC deficiency. “Once you make one diagnosis, it’s not too difficult to identify the second patient,” said Dr. Hwu.
Dr. Pearl pointed out that the movement disorders are the most prominent sign in AADC deficiency, especially the oculogyric crises. Dr. O’Malley added that this movement disorder is so rare, you don’t want to miss it. Yet, the presentation of AADC deficiency in these infants is not necessarily all that specific. “There are so many diagnoses that we consider—the celebral palsy mimickers—that fall into that category,” said Dr. O’Malley. However, she will consider AADC deficiency in any infant with hypotonia of undetermined etiology, or in a full-term baby with a normal birth history (and without clear evidence of injury) who is profoundly hypotonic and not reaching developmental milestones.
Dr. O’Malley cautioned that when children with spasticity or other movement disorders are referred to her, she carefully reevaluates the listed diagnosis. Is it really cerebral palsy? Oculogyric crises can start to give you a clue, but it is not specific for AADC deficiency. She tests for AADC deficiency frequently, but reported a low diagnosis rate. The ability to test for this genetic disorder provides the ability to identify more patients and then learn more about it.
Dr. Marks also has a low threshold for genetic testing, especially for children presenting with a movement disorder. “Even in preemies with a typical history for cerebral palsy,” stated Dr. Marks, “if the picture is not quite typical, we have found kids with a number of disorders that mimic cerebral palsy.” This is especially true in the presence of more dystonia than expected from the typical preterm infant.
Often, oculogyric crises are mistaken for seizures, said Dr. Marks. That means that epilepsy specialists may see these infants before the movement disorder physicians. Once the EEG rules out seizures, the infant will be referred to a movement disorder specialist. “Anytime you see the oculogyric crisis, you have to consider the neurotransmitter pathway,” he advised.
This convenient genetic testing panel (or “cerebral palsy-mimic panel”) has identified several children with other very rare genetic disorders, including Angelman’s syndrome, Rett syndrome, and even AADC deficiency. The roundtable 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