Aromatic L-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes.
BACKGROUND
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disorder characterised by developmental delay, motor retardation and autonomic dysfunction. Very low concentrations in cerebrospinal fluid (CSF) of homovanillic acid (HVA) and 5-hydroxy indole acetic acid (5-HIAA) are suggestive, but not specific, for this disorder. Confirmation of the diagnosis AADC deficiency is then required by enzyme activity measurement or genetic analysis.


METHODS
We describe assays for plasma AADC enzyme activity using both of its substrates, 5-hydroxytryptophan (5-HTP) and 3,4-dihydroxyphenylalanine (L-dopa). We measured AADC activity in controls, AADC deficient patients and heterozygotes.


RESULTS
AADC enzyme activity in control plasma on average is a factor 8-12 higher with L-dopa as substrate than with 5-HTP. Both substrates of AADC compete for the same active site of the enzyme resulting in equally decreased residual enzyme activities in AADC deficient patients. In AADC deficient patients, the enzyme activity towards both substrates, L-dopa and 5-HTP, are equally decreased, as are the CSF concentrations of HVA, 5-HIAA and MHPG, whereas heterozygotes have intermediate AADC activity levels.


CONCLUSIONS
The presently described assays for AADC activity measurement allow an efficient, reproducible and non-invasive way to confirm the diagnosis of AADC deficiency. Since AADC enzyme activity is much higher with L-dopa as a substrate, this method is to be preferred over activity measurement with 5-HTP as a substrate for diagnostic purposes.
Verbeek
M M
MM
Department of Neurology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. m.verbeek@cukz.umcn.nl
Geurtz
P B H
PB
Willemsen
M A A P
MA
Wevers
R A
RA
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000097:blood / Q000134:cerebrospinal fluid / Q000172:deficiency*; D002648:Child; D002675:Child, Preschool; D006579:Heterozygote; D006719:Homovanillic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D007223:Infant; D007980:Levodopa / Q000378:metabolism
D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D001142:Aromatic-L-Amino-Acid Decarboxylases; D006719:Homovanillic Acid