What Is AADC Deficiency?

Aromatic l-amino acid decarboxylase (AADC) deficiency is a genetic disorder that affects the nervous system, hindering communication between nerve cells. This condition is extremely rare, with only about 120 cases ever reported.

Patients with the inherited disease often have trouble coordinating movements, especially of the head, face, and neck.

Causes

Neurotransmitters are molecules that nerve cells use to communicate with each other and with the rest of the body. The proper production and functioning of neurotransmitters are crucial for coordinating development and a wide range of bodily processes.

AADC deficiency is caused by mutations in the DDC gene, which carries the instructions necessary to make the aromatic l-amino acid decarboxylase (AADC) enzyme. This enzyme is vital for the production of several vital neurotransmitters, including serotonin and dopamine, as well as the dopamine-derived neurotransmitters norepinephrine and epinephrine.

Mutations in the DDC gene lead to too little AADC enzyme and/or an enzyme that doesn’t work properly, ultimately leading to abnormally low production of neurotransmitters.

Symptoms

The symptoms of AADC deficiency and their severity vary substantially from person to person. In most cases, symptoms are severe and appear within the first year of life. Children with AADC deficiency usually do not hit developmental milestones such as sitting up, crawling, or talking at normal ages, or may never hit these milestones.

People with AADC deficiency usually have abnormal muscle tone, and they often experience movement disorders such as diminished movement or uncontrolled muscle contractions. Nearly all AADC deficiency patients experience oculogyric crises, in which a person’s gaze becomes fixed upward due to spasms in the muscles controlling the eyeballs.

AADC deficiency is often linked with sleep problems and with autonomic dysfunction — disturbances in the parts of the nervous system that control unconscious bodily functions, which can lead to symptoms like excessive sweating, drooping eyelids, and low blood pressure. Mental health problems and mood disorders also are common in AADC deficiency.

Diagnosis

Diagnosing AADC deficiency often involves measuring the levels of neurotransmitter-related molecules in cerebrospinal fluid (CSF) — the liquid around the brain and spinal cord. This can help detect AADC deficiency and distinguish it from other conditions that also impair neurotransmitter production but through different mechanisms.

Additional tests include taking a blood sample to determine whether the AADC enzyme is functioning properly, and genetic testing to look for disease-causing mutations in the DDC gene. Two test results indicating AADC deficiency are usually necessary to confirm a diagnosis.

Treatment

There currently is no cure for AADC deficiency, but there are treatments available to alleviate symptoms. Supplements of vitamin B6 (pyridoxine), which help the AADC enzyme to function, are often used as a first-line treatment.

These supplements typically are given in combination with medications that mimic the function of dopamine (dopamine receptor agonists) and/or therapies that prevent the breakdown of dopamine and serotonin (monoamine oxidase inhibitors).

People with AADC deficiency also can benefit from non-drug treatments like physical therapy, in which trained specialists work with patients to improve their physical functioning. Occupational therapy, which seeks to equip patients with ways to navigate the world while living with the condition, also can benefit those with the disease. For some patients, speech therapy also may be beneficial.

Experimental therapies for AADC deficiency are currently being explored. One promising treatment strategy under investigation is gene therapy, which broadly seeks to correct the function of the mutated DDC gene, usually by delivering a healthy copy of the gene to a patient’s cells.

 

Last updated: Jan. 11, 2022, by Marisa Wexler MS

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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.