title: A female case of aromatic l-amino acid decarboxylase deficiency responsive to MAO-B inhibition.
abstract: BACKGROUND
  Aromatic l-amino acid decarboxylase (AADC) deficiency is an autosomal recessive disorder, caused by defects in the DDC gene. AADC catalyzes the synthesis of the neurotransmitters dopamine and serotonin from l-dopa and 5-HT respectively. Most patients are bed ridden for life, with little response to treatment. We now report one female patient who improved her motor and cognitive function after being prescribed a MAO-B inhibitor.
  
  
  METHODS
  A five years old female presented with the typical clinical features of AADC deficiency. She was floppy, with no head control, had intermittent limb dystonia, and an upward deviation of the eyes (oculogyric crisis). This patient possessed compound heterozygous mutations in DDC (p.Trp105Cys, p.Pro129Ser), with a CSF draw indicating abnormal patterns of biogenic amine metabolites, compatible with AADC deficiency.
  
  
  RESULTS
  After her diagnosis at 3years of age, medication with levodopa and vitamin B6 failed to show any efficacy. Subsequent administration with a MAO-B inhibitor improved her psychomotor functions to the extent that at 5years of age she could walk several meters with support.
  
  
  CONCLUSIONS
  Our analyses of chemical findings, together with in silico structure predictions, lead us to hypothesize that this patient retained some AADC activity. In these cases, accurate diagnosis and early treatment should improve patient outcome.
authors.affiliation: Department of Pediatrics, Jichi Medical University, Japan.
authors.forename: Karin
authors.initials: K
authors.lastname: Kojima
authors.affiliation: Department of Neurology, Kanagawa Children's Medical Center, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Anzai
authors.affiliation: Department of Pediatrics, University of Zürich, Switzerland.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ohba
authors.affiliation: Department of Neurology, Kanagawa Children's Medical Center, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Pediatrics, Jichi Medical University, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Miyauchi
authors.affiliation: Department of Pediatrics, University of Zürich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Thöny
authors.affiliation: Department of Human Genetics, Yokohama City University, Graduate School of Medicine, Japan; Department of Biochemistry, Hamamatsu Medical University, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Human Genetics, Yokohama City University, Graduate School of Medicine, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Pediatrics, Jichi Medical University, Japan. Electronic address: hosaka@jichi.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.affiliation: Department of Pediatrics, Jichi Medical University, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamagata
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000172:deficiency* / Q000235:genetics; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009465:Neuromuscular Agents / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000627:therapeutic use; D010375:Pedigree; D011487:Protein Conformation; D016896:Treatment Outcome
chemical_list: D008996:Monoamine Oxidase Inhibitors; D009465:Neuromuscular Agents; D018697:Nootropic Agents; D001142:Aromatic-L-Amino-Acid Decarboxylases; C000595218:DDC protein, human
keywords: 3-O-methyl-l-dopa (3-OMD); Aromatic l amino acid decarboxylase (AADC) deficiency; MAO-B inhibitor; Whole exome sequencing