Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Neurology, 2010-07, Vol.75 (1), p.64

Ort / Verlag

United States

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.