Introduction
Aromatic L-amino acid decarboxylase (AADC), a vitamin B6-requiring enzyme that converts L-dopa to dopamine and 5-hydroxytryptophan to serotonin.
Deficiency of this enzyme results in developmental delay, muscular hypotonia, dystonia, involuntary movements, autonomic dysfunction, and oculogyric crises.
- Autosomal recessive inheritance
Clinical features
Characteristic movement disorders:
- Hypotonia trunk
- Oculogyric crisis
- Abnormal rotation of eyeballs with elevation of gaze
- Uncontrolled movement of head & neck
- Agitation/irritability
Less common movement disorders:
- Hypokinesia
- Hypertonia
- Tremors (involuntary movements)
- Dystonia (twisting movements)
- Athetosis (writhing movements)
- Chorea (dance-like movements)
ANS manifestations:
Due to catecholamine deficiency
- ↑ Sweating/salivation
- Ptosis
- Nasal congestion
- Unstable body temperature
- Low blood pressure
- Hypoglycemia
Other CNS symptoms:
Seizures, abnormal sleep & reflexes
Developmental symptoms:
Learning disabilities, development delays, failure to reach milestones
GI symptoms:
Reflux, diarrhoea, constipation
Diagnosis
Blood tests:
↓ AADC enzyme activity
CSF examination:
↓ Neurotransmitters
Genetic testing:
Mutated DDC gene
Management
No definitive treatment.
Dopamine agonist
↑ Dopamine
MAO inhibitors
↓ MAO activity → ↑ Neurotransmitters
Vitamin B6 (Pyridoxine)
↑ AADC enzyme activity
Melatonin:
Sleeping difficulties
Benzodiazepines/anticholinergic medications
Improve movement disorders
Multidisciplinary management:
Physical, speech & psychotherapy