title: Non-invasive urinary screening for aromatic L-amino acid decarboxylase deficiency in high-prevalence areas: a pilot study.
abstract: BACKGROUND
  The diagnosis of aromatic L-amino acid decarboxylase (AADC) deficiency, one of the pediatric neurotransmitter disorders, is classically made with plasma enzyme level or cerebrospinal fluid (CSF) neurotransmitter profile, while both are technically demanding and the latter requires the invasive lumbar puncture. So far less than 100 cases have been reported worldwide with 20% from Taiwan. It was postulated that the condition might have been under-diagnosed among Chinese populations and a non-invasive screening tool should be developed in areas with high prevalence.
  
  
  METHODS
  Urine metabolic profiles performed by gas chromatography-mass spectrometry (GC-MS) in a 31-month period were retrospectively reviewed: those with vanilmandelic acid concentration lower than one percentile plus the presence of 3-o-methyldopa were defined as positive and the patients were further evaluated.
  
  
  RESULTS
  Among 1046 metabolic profiles (from 845 patients) reviewed, 3 profiles from 2 patients were screened positive: both cases had compatible CSF neurotransmitter profiles and the diagnosis was further confirmed by genetic analysis of DDC gene. 13 negative urinary metabolic profiles from 7 patients who had CSF neurotransmitters analyzed were identified as controls: all 7 CSF neurotransmitter profiles were not compatible for AADC deficiency.
  
  
  CONCLUSIONS
  The GC-MS-based urine metabolic profiling was shown to be a satisfactory screening tool for AADC deficiency. Further confirmation can be performed by mutation analysis in the DDC gene, thus avoiding risks of lumbar puncture. We advocate all ethnic Chinese patients presenting with dystonia have their urine organic acids analyzed before proceeding to CSF neurotransmitters analysis.
authors.affiliation: Department of Pathology, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Han-Chih Hencher
authors.initials: HC
authors.lastname: Lee
authors.forename: Chi-Kong
authors.initials: CK
authors.lastname: Lai
authors.forename: Kin-Cheong Eric
authors.initials: KC
authors.lastname: Yau
authors.forename: Tak-Shing
authors.initials: TS
authors.lastname: Siu
authors.forename: Chloe Miu
authors.initials: CM
authors.lastname: Mak
authors.forename: Yuet-Ping
authors.initials: YP
authors.lastname: Yuen
authors.forename: Kwok-Yin
authors.initials: KY
authors.lastname: Chan
authors.forename: Sidney
authors.initials: S
authors.lastname: Tam
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
authors.forename: Albert Yan-Wo
authors.initials: AY
authors.lastname: Chan
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000652:urine; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000172:deficiency / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D007223:Infant; D008297:Male; D010865:Pilot Projects; D015995:Prevalence
chemical_list: D001142:Aromatic-L-Amino-Acid Decarboxylases