Disorder Description
Neurotransmitters: the naturally occurring chemical substances in the brain which are used to transfer messages between different brain cells.
AADC is an essential enzyme, which is involved in the decarboxylation of the aromatic amino acids L-dopa and 5-hydroxytryptophan. This enzyme forms the neurotransmitters dopamine and serotonin, and when the enzyme is defective, the passage and signaling of two of the brain's main neurotransmitters needed for daily living is disrupted.
Dopamine can be further converted into the neurotransmitters of norepinephrine (non-adrenaline) and epinephrine (adrenaline), which are also deficient in the central nervous system and periphery in this disorder.
Signs and Symptoms
AADC Deficiency presents early in life, usually within the first year. The symptoms of AADC vary in degree of severity; ranging from mild, moderate, or severe from case to case. In the absence of treatment, the majority of children who are affected show minimal motor development.
Some of the presentation of signs and symptoms of AADC are as follows:
In infancy especially:
- Difficulties feeding
- Autonomic dysfunction
- Hypotonia (Decreased muscle tone)
Motor and autonomic dysfunctions:
- Rigidity and stiffness
- Abnormal eye movements
- Hypersalivation
- Tongue thrusting
- Excessive or disrupted sleep ( with variation or improvement of neurologic symp toms after sleep)
- Limb dystonia (disorder of muscle control)
- Delays in development
- Parkinsonism
- Instability of temperature
- Tremors
- Swallowing and feeding difficulties
- Nasal congestion
- Lack of speech
- Gastrointestinal symptoms
- Head drops
- Droopy eyelids (Ptosis)
- Involuntary deviation of the head and neck (Torticollis)
- Rattled breathing (Stridor)
- Chorea (abnormal involuntary movement)
- Excessive sweating
- Emotional lability and Dysphoria
- Spasmodic attack and upward fixation of the eyes (oculogyric crises)
Testing
An AADC diagnosis is commonly based upon the following testing procedures:
1) Lumbar Puncture (Spinal Tap)
This test is preferred, as it can distinguish between several diseases that present with similar symptoms. A sample of cerebrospinal fluid (CSF) is taken from a child suspected of having AADC deficiency (or other similar dopamine related disease). Screening of the cerebrospinal fluid should show the following characteristic results for AADC:
a) Elevated levels of L-dopa, 5-hydroxytryptophan (5HTP) and 3-orthomethyldopa (3-o-md).
b) Decreased levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic (5HIAA) levels
2) Blood Tests
- Plasma Enzyme Assay
- DNA Analysis
Blood samples can show whether or not there is low / absent enzyme of involvement in the decarboxylation of aromatic amino acid. This procedure can be used to confirm findings if a lumbar puncture has already been performed, or to confirm an AADC diagnosis if the child refuses to have a lumbar puncture / spinal tap performed. Extracted DNA can allow for sequencing of the coding for the AADC gene (mapped to chromosome 7p12.1-p12.3) to determine any mutations-thus confirming a diagnosis.
Treatment
Currently, AADC treatment involves a variety of medications that exhibit varying success depending on the patient. These medications could include any or any combination of the following:
Dopamine Receptor Agonists- artificial forms of dopamine that mimic their naturally occurring counterparts by attaching and stimulating the dopamine receptors in the brain.
Antiepileptics- used for the treatment of seizures.
Anticholinergic Agents- theoretically, used to improve balance between acetylcholine and dopamine.
Serotonergic Medications
Monoamine Oxidase Inhibitor- used to inhibit the monoamine oxidase enzyme, which would normally break down dopamine and serotonin. This is because of the already very small amount of those neurotransmitters that characterize the AADC disorder.
Gastrointestinal Medications
Location
While we are based in Massachusetts, we gladly assist families suffering from AADC all across the United States!