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. Neurology (R) 2010; 75: 64-71

Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency / L. Brun, L. Ngu, W. Keng, G. Ch'Ng, Y. Choy, W. Hwu, W. Lee, M. Willemsen, M. Verbeek, T. Wassenberg, L. Regal, S. Orcesi, D. Tonduti, P. Accorsi, H. Testard, J. Abdenur, S. Tay, G. Allen, S. Heales, I. Kern, M. Kato, A. Burlina, C. Manegold, G. Hoffmann, N. Blau. - In: NEUROLOGY. - ISSN 0028-3878. - 75:1(2010), pp. 64-71. [10.1212/WNL.0b013e3181e620ae]

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

D. Tonduti;
2010

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. Neurology (R) 2010; 75: 64-71
Settore MED/39 - Neuropsichiatria Infantile
2010
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/938709
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