Aromatic l-amino acid decarboxylase (AADC) deficiency is a genetic disorder that is caused by communication problems between nerve cells in the brain and other parts of the body. As a consequence, AADC deficiency patients typically develop movement disorders and autonomic dysfunction. They also may experience seizures.

Seizures in AADC deficiency

Because AADC deficiency is a rare condition and seizures do not occur in every patient, they are not well-documented. Generalized tonic-clonic seizures that are characterized by stiff muscles and jerking movements have been reported in AADC deficiency patients.

The movement disorders that occur in AADC deficiency lead to unpredictable involuntary movements (chorea) and involuntary muscle contractions that cause repetitive twisting (dystonia). These spastic movements may resemble seizures and are sometimes mistaken as seizures.

How AADC deficiency causes seizures

Nerve cells in the brain communicate with each other through electrical signals. Neurotransmitters also are involved in this process. As an electrical signal travels from one nerve cell to the next, the nerve cell sending the signal (called a presynaptic neuron) releases a neurotransmitter into the synaptic cleft. A synaptic cleft is a space between nerve cells across which a nerve impulse is transmitted. The neurotransmitter then binds to receptors found on the surface of the nerve cell receiving the signal (the so-called postsynaptic neuron). This binding translates into an electric signal so that the postsynaptic neuron gets “excited.” In a similar process, nerve cells also can inhibit the activity of other nerve cells.

A seizure occurs when the electric firing of nerve cells is out of control. When too many excitatory signals stimulate too many nerve cells, a seizure occurs. A healthy balance of inhibitory and excitatory signals typically prevents seizures.

AADC deficiency is caused by a mutation in the dopa decarboxylase (DDC) gene, which provides instructions to build the AADC enzyme. This enzyme is involved in the synthesis of the neurotransmitters dopamine and serotonin. A mutation in the DDC gene leads either to reduced production of AADC enzyme or decreased activity of the enzyme. As a consequence, dopamine and serotonin levels are too low in ADDC deficiency patients. It is not exactly understood how AADC deficiency causes seizures, but insufficient levels of certain neurotransmitters seem to create an imbalance between excitatory and inhibitory neuronal signals, favoring the development of seizures.

Treatment of seizures

Seizures in AADC deficiency usually are treated with antiepileptic medications such as phenobarbital, carbamazepine, phenytoin, clonazepam, clobazam, and valproic acid.

 

Last updated: Sept. 26, 2019.

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AADC News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare providers with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.