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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-34893

Brun, L; Ngu, L H; Keng, W T; Ch'ng, G S; Choy, Y S; Hwu, W L; Lee, W T; Willemsen, M A A P; Verbeek, M M; Wassenberg, T; Régal, L; Orcesi, S; Tonduti, D; Accorsi, P; Testard, H; Abdenur, J E; Tay, S; Allen, G F; Heales, S; Kern, I; Kato, M; Burlina, A; Manegold, C; Hoffmann, G F; Blau, N (2010). Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency. Neurology, 75(1):64-71.

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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. 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.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:July 2010
Deposited On:16 Jul 2010 08:38
Last Modified:09 Dec 2012 22:01
Publisher:American Academy of Neurology
ISSN:0028-3878
Publisher DOI:10.1212/WNL.0b013e3181e620ae
PubMed ID:20505134
Citations:Google Scholar™
Scopus®. Citation Count: 33

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