Timothy John Feyma, MD, Bruria Ben Zeev, and Thomas Opladen, MD, describe management options that are available for AADC deficiency
Feyma: I think the current management that exists increases comfort but doesn’t really make the patient a lot better. I think that we might help them from having less tight, stiffening movements that bother them, but it’s not going to help them sit up, or keep their head up, or walk. So, we’re really still kind of stuck in a very basic treatment.
Ben Zeev: The treatment is—the frustrating part of the treatment of AADC deficiency is, it’s complicated on one hand, and it’s not very helpful on the other hand.
Ben Zeev: I must say that from my experience and from the literature, most of these treatments are—their main role is to reduce the number and the severity of the paroxysmal events, but they hardly ever have any effect on these children’s development.
Opladen:The standard drug treatment is coming from the biochemic background, so when you have an AADC deficiency, you try to replace somehow the deficient effect of dopamine and serotonin—and it’s not so straightforward, like you could do it in any other biosynthesis defect of L-DOPA, dopamine, for example. So what you need to do, you need to—you try to first of all improve or enhance, if this is possible, the enzymatic activity by adding the co-factor of the AADC enzyme, which is pyridoxine or basically pyridoxal phosphate in the final word. The second thing is you can add drugs which inhibit the degradation of these two metabolites in the synaptic cleft—here we have monoamine oxidase inhibitors—and they can basically keep these two metabolites, these two neurotransmitters in the synaptic cleft, and improve direction. And, the third approach is to mimic the dopamine effect using dopamine receptor agonists. We can say this treatment is always a combined treatment, so you can in the end decide with your patient or according to the clinical presentation of your patient what to do first—what kind of drug to introduce first—but in the end, you will have multiple drugs in treatment.