Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disorder caused by mutations in the DDC gene.
It is associated with impaired synthesis of dopamine and serotonin neurotransmitters.
Symptoms typically emerge in infancy: developmental delays, movement disorders such as dystonia, oculogyric crises, autonomic dysfunction such as ptosis, temperature instability, and sleep disturbances.
Neurological Symptoms
Oculogyric crises: Involuntary upward eye movements, often triggered by stress or fatigue.
Dystonia and hypokinesia: Abnormal muscle contractions and reduced movement, worsening with tiredness.
Developmental delays with motor and cognitive impairments, including difficulty sitting or walking.
Autonomic Dysfunction Temperature instability, hypoglycemia, nasal congestion, and excessive sweating.
Gastrointestinal issues like reflux, vomiting, and feeding difficulties.
Sleep disturbances (insomnia or excessive sleepiness).
Caused by biallelic mutations in the DDC gene, resulting in deficient AADC enzyme activity.
This enzyme converts L-DOPA to dopamine and 5-HTP to serotonin; its deficiency disrupts neurotransmitter signaling.
Genetic testing: Confirms DDC gene mutations.
Cerebrospinal fluid (CSF) analysis: Reveals low levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), alongside elevated 3-O-methyldopa (3-OMD).
Enzyme assay: Reduced AADC activity in plasma.
Symptomatic Management Dopamine agonists (e.g., rotigotine) and MAO inhibitors (e.g., selegiline) to boost neurotransmitter activity.
Physical, occupational, and speech therapies.
Gene Therapy Eladocagene exuparvovec (Upstaza): for severe cases in patients aged ≥18 months-it Restores dopamine production via viral vector delivery of functional DDC genes.
Outcomes vary widely.
Early diagnosis and targeted therapies may improve motor function and quality of life, but many patients experience lifelong disabilities.