Summary
Aromatic l-amino acid decarboxylase (AADC) deficiency is a very rare genetic disorder. Affected individuals can appear normal at birth, but most will develop symptoms during the first months of life. Symptoms can include abnormal eye movements, movement disorders (especially dystonia) and autonomic dysfunction (excessive sweating, temperature instability, drooping eyelids [ptosis}, nasal congestion and a low level of glucose in the blood [hypoglycemic episodes]). Sleep disturbances are common and may include difficulty sleeping, difficulty staying awake or both. Mood disturbances such as irritability and anxiety are also frequently observed. Brain MRI results are typically normal or may show non-specific abnormalities. Seizures are rare. People with AADC deficiency have a decreased activity of aromatic l-amino acid decarboxylase, an enzyme involved in the building (synthesis) of neurotransmitters (dopamine and serotonin), which are responsible for the communication between neurons in the nervous system.
Medication is available to manage the symptoms, but response to treatment greatly varies among affected individuals, and an optimal treatment regimen can be difficult to achieve. The gene therapy eladocagene exuparvovec (Upstaza) has been approved in the European Union and United Kingdom for individuals aged 18 months and older diagnosed with AADC deficiency, confirmed clinically, molecularly and genetically, who have severe disease. This treatment is not currently approved by the FDA for use in the United States.
