Clinical and therapeutic observations in aromatic L-amino acid decarboxylase deficiency.
OBJECTIVE
To elucidate the phenotype in aromatic L-amino acid decarboxylase (AADC) deficiency, a rare autosomal recessive disorder of neurotransmitter synthesis, and report preliminary treatment observations with directed therapy of the associated neurotransmitter deficiencies.


BACKGROUND
AADC is a required enzyme in dopamine, norepinephrine, epinephrine, and serotonin biosynthesis. Five patients have been previously reported. Responses to treatment interventions in these patients have been mixed.


METHODS
Clinical and biochemical evaluation and therapeutic trials were performed in two children over a 26-month period.


RESULTS
Characteristic features included axial hypotonia, hypokinesia, and athetosis, with superimposed episodes of ocular convergence spasm, oculogyric crises, dystonia, and limb rigidity. Catecholamine deficiency was manifest by ptosis, nasal congestion, paroxysmal diaphoresis, temperature instability, and blood pressure lability. Abnormal sleep, feeding difficulties, and esophageal reflux were typical. Significant therapeutic benefit was observed in one child with a combination of pergolide, trihexyphenidyl, and tranylcypromine. Preliminary trials using serotonin receptor agonists or reuptake inhibitors resulted in adverse effects.


CONCLUSIONS
The movement disorder in AADC deficiency, particularly the characteristic eye movement abnormalities, should facilitate the identification of patients with this rare but possibly underrecognized disorder. Directed therapy of the underlying dopamine and norepinephrine deficiency may be beneficial in some cases.
Swoboda
K J
KJ
Division of Genetics, Children's Hospital and Harvard Medical School, Boston, MA, USA.
Hyland
K
K
Goldstein
D S
DS
Kuban
K C
KC
Arnold
L A
LA
Holmes
C S
CS
Levy
H L
HL
D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood* / Q000235:genetics; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000172:deficiency*; D001921:Brain / Q000503:physiopathology; D002395:Catecholamines / Q000097:blood*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype
D002395:Catecholamines; D001142:Aromatic-L-Amino-Acid Decarboxylases