Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency
Journal
Neurology
Journal Volume
75
Journal Issue
1
Pages
64-71
Date Issued
2010
Author(s)
Brun L.
Ngu L.H.
Keng W.T.
Ch'Ng G.S.
Choy Y.S.
Willemsen M.A.A.P.
Verbeek M.M.
Wassenberg T.
R?gal 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.
Abstract
To describe the current treatment; clinical, biochemical, and molecular findings; and clinical follow-up of patients with aromatic l-amino acid decarboxylase (AADC) deficiency. 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. 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%). 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.
SDGs
Publisher
Lippincott Williams and Wilkins
Type
journal article