title: Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency.
abstract: OBJECTIVE
  To describe the current treatment; clinical, biochemical, and molecular findings; and clinical follow-up of patients with aromatic l-amino acid decarboxylase (AADC) deficiency.
  
  
  METHODS
  Clinical and biochemical data of 78 patients with AADC deficiency were tabulated in a database of pediatric neurotransmitter disorders (JAKE). A total of 46 patients have been previously reported; 32 patients are described for the first time.
  
  
  RESULTS
  In 96% of AADC-deficient patients, symptoms (hypotonia 95%, oculogyric crises 86%, and developmental retardation 63%) became clinically evident during infancy or childhood. Laboratory diagnosis is based on typical CSF markers (low homovanillic acid, 5-hydroxyindoleacidic acid, and 3-methoxy-4-hydroxyphenolglycole, and elevated 3-O-methyl-l-dopa, l-dopa, and 5-hydroxytryptophan), absent plasma AADC activity, or elevated urinary vanillactic acid. A total of 24 mutations in the DDC gene were detected in 49 patients (8 reported for the first time: p.L38P, p.Y79C, p.A110Q, p.G123R, p.I42fs, c.876G>A, p.R412W, p.I433fs) with IVS6+ 4A>T being the most common one (allele frequency 45%).
  
  
  CONCLUSIONS
  Based on clinical symptoms, CSF neurotransmitters profile is highly indicative for the diagnosis of aromatic l-amino acid decarboxylase deficiency. Treatment options are limited, in many cases not beneficial, and prognosis is uncertain. Only 15 patients with a relatively mild form clearly improved on a combined therapy with pyridoxine (B6)/pyridoxal phosphate, dopamine agonists, and monoamine oxidase B inhibitors.
authors.affiliation: Division of Clinical Chemistry and Biochemistry, University Children's Hospital, Steinwiesstrasse 75, CH-8032 Zürich, Switzerland. .
authors.forename: L
authors.initials: L
authors.lastname: Brun
authors.forename: L H
authors.initials: LH
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authors.forename: W T
authors.initials: WT
authors.lastname: Keng
authors.forename: G S
authors.initials: GS
authors.lastname: Ch'ng
authors.forename: Y S
authors.initials: YS
authors.lastname: Choy
authors.forename: W L
authors.initials: WL
authors.lastname: Hwu
authors.forename: W T
authors.initials: WT
authors.lastname: Lee
authors.forename: M A A P
authors.initials: MA
authors.lastname: Willemsen
authors.forename: M M
authors.initials: MM
authors.lastname: Verbeek
authors.forename: T
authors.initials: T
authors.lastname: Wassenberg
authors.forename: L
authors.initials: L
authors.lastname: Régal
authors.forename: S
authors.initials: S
authors.lastname: Orcesi
authors.forename: D
authors.initials: D
authors.lastname: Tonduti
authors.forename: P
authors.initials: P
authors.lastname: Accorsi
authors.forename: H
authors.initials: H
authors.lastname: Testard
authors.forename: J E
authors.initials: JE
authors.lastname: Abdenur
authors.forename: S
authors.initials: S
authors.lastname: Tay
authors.forename: G F
authors.initials: GF
authors.lastname: Allen
authors.forename: S
authors.initials: S
authors.lastname: Heales
authors.forename: I
authors.initials: I
authors.lastname: Kern
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: A
authors.initials: A
authors.lastname: Burlina
authors.forename: C
authors.initials: C
authors.lastname: Manegold
authors.forename: G F
authors.initials: GF
authors.lastname: Hoffmann
authors.forename: N
authors.initials: N
authors.lastname: Blau
mesh_terms: D000293:Adolescent; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000134:cerebrospinal fluid* / Q000172:deficiency*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid / Q000172:deficiency; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018377:Neurotransmitter Agents; D001142:Aromatic-L-Amino-Acid Decarboxylases