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Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency (e-Pub ahead of print) (CME).
Brun, L.; Ngu, L.H. MRCP; Keng, W.T. MRCP; Ch'ng, G.S. MRCPch; Choy, Y.S. MD; Hwu, W.L. MD, PhD; Lee, W.T. MD; Willemsen, M.A.A.P. MD, PhD; Verbeek, M.M. PhD; Wassenberg, T. MD; Regal, L. MD; Orcesi, S. MD; Tonduti, D. MD; Accorsi, P. MD; Testard, H. MD; Abdenur, J.E. MD; Tay, S. MD; Allen, G.F. BSc; Heales, S. PhD; Kern, I. MD, PhD; Kato, M. MD; Burlina, A. MD; Manegold, C. MD; Hoffmann, G.F. MD; Blau, N. PhD
[Article] Neurology. 75(1):64-71, July 6, 2010.

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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.