Aromatic L-Amino Acid Decarboxylase Deficiency with Hyperdopaminuria. Clinical and Laboratory Findings in Response to Different Therapies

Abstract

Aromatic L-amino acid decarboxylase (AADC - E.C. 4.1.1.28) converts L-dopa to dopamine and 5-hydroxytryptophan to serotonin. Inherited deficiency of this enzyme leads to decreased brain levels of these neurotransmitters. Clinically this results in the development of a progressive neurometabolic disorder characterized by severe hypotonia, dystonic and choreoathetoid movements, oculogyric crises, and hypothermia from infancy. Here we describe the clinical, biochemical and molecular details of two affected brothers, one of whom, despite the lack of AADC, presented with hyperdopaminuria. In addition, we detail his reactions to treatment with dopaminergic agonists, monoamine oxidase inhibitors and pyridoxine.

Key words

Aromatic L-Amino Acid Decarboxylase Deficiency - Neurotransmitters - Hyperdopaminuria - L-Dopa

References

• 1 Abeling N GGM, Van Gennip A H, Barth P G, van Cruchten A, Westra M, Wijburg F A. Aromatic amino acid decarboxylase deficiency: a new case with a mild clinical presentation and unexpected laboratory findings.  J Inher Metab Dis. 1998;  21 240-242
• 2 Abeling N GGM, Bräutigam C, Hoffmann G F, Barth P G, Wevers R A, Jaeken J, Fiumara A, Knust A, Van Gennip A H. Pathobiochemical implications of hyperdopaminuria in patients with aromatic amino acid decarboxylase deficiency.  J Inher Metab Dis. 2000;  23 325-328
• 3 Bräutigam C, Wevers R A, Jansen R JT. et al . Biochemical hallmarks of tyrosine hydroxylase deficiency.  Clin Chem. 1998;  44 1897-1904
• 4 Bräutigam C, Wevers R A, Hyland K, Sharma R K, Knust A, Hoffmann G F. The influence of L-Dopa on methylation capacity in aromatic L-amino acid decarboxylase deficiency: Biochemical findings in two patients.  J Inher Metab Dis. 2000;  23 321-324
• 5 Fiumara A, Wevers R, Barone R, Lagae L, Stoltenborg B, Nigro F, Jaeken J. Aromatic L-amino acid decarboxylase deficiency: the first Italian case.  J Inher Metab Dis. 1998;  21 (Suppl 2) 5
• 6 Hyland K, Clayton P T. Aromatic amino acid decarboxylase deficiency in twins.  J Inher Metab Dis. 1990;  13 301-304
• 7 Hyland K, Surtees R AH, Rodeck C, Clayton P T. Aromatic amino acid decarboxylase deficiency: Clinical features, diagnosis and treatment of a new inborn error of neurotransmitter amine synthesis.  Neurology. 1992;  42 1980-1988
• 8 Hyland K, Clayton P T. Aromatic L-amino acid decarboxylase deficiency: Diagnostic methodology.  Clin Chem. 1992;  38 2405
• 9 Korenke G C, Christen H J, Hyland K, Hunneman D H, Hanefeld F. Aromatic L-amino acid decarboxylase deficiency. An extrapyramidal movement disorder with oculogyric crises.  Eur J Paed Neurol. 1997;  2/3 67-71
• 10 Maller A, Hyland K, Milstien S, Biaggioni I, Butler I J. Aromatic L-amino acid decarboxylase deficiency: Clinical features, diagnosis and treatment of a second family.  J Child Neurol. 1997;  12 349-354
• 11 Nagatsu T. Genes for human catecholamine-synthesizing enzymes.  Neurosci Res. 1991;  12 315-345
• 12 Swoboda K J, Hyland K. Clinical and therapeutic observation in aromatic amino-acid decarboxylase deficiency.  Neurology. 1999;  53 1205-1211