Causes of AADC Deficiency

Last updated Jan. 6, 2022, by Marisa Wexler, MS

✅ Fact-checked by Inês Martins, PhD


Genetic mutations cause aromatic L-amino acid decarboxylase (AADC) deficiency, an inherited disorder that disrupts communication between the brain and other parts of the body, resulting in developmental delays and other symptoms that begin at a young age.

Neurons, or nerve cells, communicate with each other using chemical messengers called neurotransmitters. Dopamine and serotonin are two vital neurotransmitters involved in a wide range of bodily processes, from regulating mood and digestion to coordinating movement.

AADC deficiency is caused by mutations in the dopa decarboxylase (DDC) gene, which carries the instructions to make the aromatic L-amino acid decarboxylase (AADC) enzyme. This enzyme is needed to make both dopamine and serotonin.

Dopamine and serotonin are both produced in two-step processes. Dopamine synthesis starts with an amino acid (the building block of proteins) called tyrosine, which is first converted to L-dopa. The first step of serotonin synthesis, meanwhile, begins with the conversion of another amino acid, called tryptophan, to 5-hydroxytryptophan.

The AADC enzyme then facilitates the final step in the process of converting L-dopa and 5-hydroxytryptophan to dopamine and serotonin, respectively. It does that by removing a molecular structure called a carboxyl group from the intermediate metabolites — hence the name decarboxylase.

Mutations in the DDC gene lead to the production of too little AADC enzyme and/or an enzyme that does not work properly. The lack of functional AADC results in reduced dopamine and serotonin levels, as well as lower levels of epinephrine and norepinephrine — two neurotransmitters that derive from dopamine — which is what ultimately leads to the symptoms of AADC deficiency.

Inheritance of AADC deficiency

Everyone inherits two copies of the DDC gene, one from each biological parent. AADC deficiency is inherited in an autosomal recessive manner, meaning that the disease only develops if both copies of the DDC gene are mutated.

Individuals who have just one mutated copy of the gene are called carriers of AADC deficiency. Carriers usually do not exhibit any symptoms, but they may pass the disease-causing gene on to their biological children.

 


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