Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency

Brun L 1 , Ngu LH 2 , Keng WT 2 , Ch'ng GS 2 , Choy YS 3 , Hwu WL 4 Show all authors , Lee WT 4 , Willemsen MA 5 , Verbeek MM 6 , Wassenberg T 7 , Regal L 8 , Orcesi S 9 , Tonduti D 9 , Accorsi P 10 , Testard H 11 , Abdenur JE 12 , Tay S 13 , Allen GF 14 , Heales S 14 , Kern I 15 , Kato M 16 , Burlina A 17 , Manegold C 18 , Hoffman GF 18 , Blau N 19

Affiliations 

  • 1 Division of Clinical Chemistry and Biochemistry, University Children’s Hospital, Zurich, Switzerland
  • 2 Genetic Department, Kuala Lumpur Hospital, Jalan Pahang, Kuala Lumpur, Malaysia
  • 3 Prince Court Medical Centre, Kuala Lumpur, Malaysia
  • 4 Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
  • 5 Department of Pediatric Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
  • 6 Donders Centre for Brain, Cognition and Behaviour, and Departments of Neurology and Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
  • 7 Departments of Neurology and Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
  • 8 Pediatrics-Metabolic Center, University Hospital Leuven, Leuven, Belgium
  • 9 Department of Child Neurology and Psychiatry, IRCCS C. Mondino Institute of Neurology Foundation, Pavia
  • 10 Department of Child Neurology and Psychiatry, Spedali Civici, Brescia, Italy
  • 11 Centre Hospitalier Intercommunal Annemasse, Service de Pediatrie et de Neonatalogie, Annemasse, France
  • 12 Division of Metabolic Disorders, CHOC Children’s, Orange, CA
  • 13 Division of Pediatric Neurology and Developmental Pediatrics, Department of Pediatrics, National University of Singapore and National University Hospital, Singapore
  • 14 Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK
  • 15 Pediatric Metabolism, University Children’s Hospital, Geneva, Switzerland
  • 16 Department of Pediatrics, Yamagata University Hospital, Yamagata, Japan
  • 17 Division of Metabolic Disorders, Department of Pediatrics, University Hospital, Padua, Italy
  • 18 Zentrum fur Kinder- und Jugendmedizin der Universitat Heidelberg, Heidelberg, Germany.
  • 19 Nenad Blau, Division of Clinical Chemistry and Biochemistry, University Children’s Hospital, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland. [email protected]
PMID: 20505134 DOI: 10.1212/WNL.0b013e3181e620ae

Abstract

Neurology. 2010 Jul 6;75(1):64-71
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.
METHOD: 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%).
CONCLUSION: 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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