DDC gene
Also known as: AADC deficiency; Dopa decarboxylase deficiency; DDC deficiency
– OMIM#608643 https://omim.org/entry/608643
1. The Disease:
A rare, severe, genetic neurometabolic disorder associated with clinical manifestations related to impaired synthesis of dopamine, noradrenaline, adrenaline, and serotonin. Clinical manifestations are typically characterized by early-onset muscular hypotonia, movement disorders (oculogyric crisis, dystonia), developmental delay, ptosis, and non-motor symptoms (sleep disturbance, irritability, excessive sweating, and nasal congestion).
2. The symptoms:
AADC deficiency typically presents in infancy with muscular hypotonia, oculogyric crises, and developmental delay. Lack of early signs or symptoms does not exclude the diagnosis.
Thermoregulation disturbances, autonomic dysfunction, sleep disorders, dystonia, nasal congestion, feeding problems and intellectual disability are additional disease features.
Age of onset of initial symptoms ranges from neonatal period to 12 months (mean 2-3 months). Most published patients have severe phenotype with profound motor developmental impairment while some present mild to moderate phenotype with ability to walk independently and having functional independence in daily activities. It has been suggested that symptoms can evolve with age.
3. Actions to take in case of early diagnosis:
- Biochemical correlation is important by determination of biogenic amines in cerebrospinal fluid (CSF) and enzyme activity essay in plasma and mutational analysis. Additionally, measurement of 3-O-methyldopa (3-OMD) in dried blood spot in newborn screening is proposed to be implemented in some programs.
- AADCD is a lifelong disease requiring lifetime management and regular follow-up with a Paediatric Neurology Center Management is provided by multidisciplinary team.
- The treatment of AADC deficiency is challenging since symptoms are refractory particularly in severe cases. A complex treatment regimen including dopamine agonists, monoamine oxidase inhibitors, pyridoxine phosphate, anticholinergic and antiepileptic drugs are required.
- Various supportive therapeutic approaches (physiotherapy, speech therapy) are recommended.
- In clinical trials, gene therapy has demonstrated clinical improvement (reduced frequency of oculogyric crises, weight recovery, and improvement in the ability to sit, walk, and talk over a five-year period).
- Genetic counselling should be offered to at-risk family members.
4. For more information:
Biblio : Pearson TS, Gupta N, San Sebastian W, et al. Gene therapy for aromatic L-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons. Nat Commun. 2021;12(1):4251. PMID:34253733.