aromatic L-amino acid decarboxylase deficiency

Aromatic L-amino acid decarboxylase deficiency (often called AADC deficiency) is a very rare neurometabolic condition that disrupts the brain’s ability to produce the neurotransmitters dopamine and serotonin. The disorder results from disease-causing changes in the DDC gene, which provides instructions for the AADC enzyme that converts precursor molecules into active neurotransmitters. Symptoms usually begin in infancy and involve the nervous system and the body’s automatic (autonomic) functions. Because it affects fewer than one in a million people worldwide, many families and clinicians may be unfamiliar with the condition, making early recognition challenging. Severity and symptoms vary widely between individuals.

AADC deficiency primarily affects motor control and autonomic regulation. Early in life, many babies have low muscle tone that makes them feel floppy, diminished spontaneous movement, and characteristic oculogyric crises in which the eyes roll upward for minutes to hours. Over time, persistent movement problems such as dystonia, limb rigidity, athetosis, and tremor can develop, often accompanied by eyelid drooping (ptosis) and episodes of involuntary head turning (torticollis). Autonomic features include temperature instability, sweating abnormalities, nasal congestion, and gastrointestinal issues such as gastroesophageal reflux, constipation, or diarrhea. Feeding difficulties, irritability, emotional lability, sleep disturbance, and episodes of apnea are also reported. Not all individuals experience all features, and the clinical spectrum ranges from mild motor delay to severe, life-threatening complications such as cardiorespiratory arrest.

The condition is caused by pathogenic variants in the DDC gene. This gene encodes the aromatic L-amino acid decarboxylase enzyme, a key catalyst in the final step of producing dopamine and serotonin. When the enzyme is deficient or not functioning properly, levels of these neurotransmitters drop, leading to the neurological and autonomic symptoms seen in affected individuals. AADC deficiency is inherited in an autosomal recessive pattern, meaning a child must receive one altered copy of the gene from each parent to develop the disorder. Parents who each carry a single non-working copy are usually healthy but have a 25 percent chance with each pregnancy to have an affected child. Because the chance that both parents carry the same rare variant is higher when they share common ancestors, the condition can be more frequent in families with related parents. Carrier testing and genetic counseling are recommended for relatives who may wish to understand their own risks.

Currently, management focuses on supportive care and symptom management tailored to each individual. Multidisciplinary care teams commonly include neurologists, rehabilitation specialists, nutritionists, and respiratory therapists. Physical and occupational therapy aim to optimize mobility and prevent contractures, while speech and feeding therapy help address swallowing difficulties and reduce the risk of aspiration. Medications directed by specialists may lessen dystonia, control reflux, or improve sleep, although responses vary. Long-term management includes regular surveillance for respiratory complications, nutritional status, and autonomic dysfunction so that emerging problems can be addressed promptly. Families are encouraged to discuss evolving treatment options and investigational therapies in clinical trials with their healthcare team.

Outcomes depend on many factors including the specific genetic variants, the severity of neurotransmitter deficiency, and timely access to specialized care. Some children remain medically fragile and require lifelong supportive therapies, while others achieve limited independent mobility or communication skills. Respiratory infections and autonomic crises can be life-threatening, especially in early childhood, but proactive monitoring and modern supportive interventions have improved survival and quality of life for many families. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and genetic counselors to plan ongoing care, anticipate future needs, and explore participation in natural history studies that inform new treatments.

Several clinical trials are currently investigating gene therapy and other novel approaches designed to increase dopamine and serotonin production or stabilize autonomic function. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility and enrollment considerations.