A female case of aromatic l -amino acid decarboxylase deficiency responsive to MAO-B inhibition

• Published in: Brain & development (Tokyo. 1979) Vol. 38; no. 10; pp. 959 - 963
• Main Authors: Kojima, Karin, Anzai, Rie, Ohba, Chihiro, Goto, Tomohide, Miyauchi, Akihiko, Thöny, Beat, Saitsu, Hirotomo, Matsumoto, Naomichi, Osaka, Hitoshi, Yamagata, Takanori
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2016
• Subjects: 3-O-methyl-l-dopa (3-OMD); Amino Acid Metabolism, Inborn Errors - drug therapy; Amino Acid Metabolism, Inborn Errors - enzymology; Amino Acid Metabolism, Inborn Errors - genetics; Amino Acid Metabolism, Inborn Errors - physiopathology; Aromatic l amino acid decarboxylase (AADC) deficiency; Aromatic-L-Amino-Acid Decarboxylases - deficiency; Aromatic-L-Amino-Acid Decarboxylases - genetics; Child, Preschool; DNA Mutational Analysis; Female; Humans; MAO-B inhibitor; Monoamine Oxidase Inhibitors - therapeutic use; Motor Activity - drug effects; Motor Activity - genetics; Motor Activity - physiology; Neurology; Neuromuscular Agents - therapeutic use; Nootropic Agents - therapeutic use; Pedigree; Protein Conformation; Treatment Outcome; Whole exome sequencing; MAO-B inhibitor; 3-O-methyl- l-dopa (3-OMD); Whole exome sequencing; Aromatic l amino acid decarboxylase (AADC) deficiency; 3-O-methyl-l-dopa (3-OMD)
• ISSN: 0387-7604; 1872-7131
• DOI: 10.1016/j.braindev.2016.06.002

Abstract Background Aromatic l -amino acid decarboxylase (AADC) deficiency is an autosomal recessive disorder, caused by defects in the DDC gene. AADC catalyzes the synthesis of the neurotransmitters dopamine and serotonin from l -dopa and 5-HT respectively. Most patients are bed ridden for life, with little response to treatment. We now report one female patient who improved her motor and cognitive function after being prescribed a MAO-B inhibitor. Case A five years old female presented with the typical clinical features of AADC deficiency. She was floppy, with no head control, had intermittent limb dystonia, and an upward deviation of the eyes (oculogyric crisis). This patient possessed compound heterozygous mutations in DDC (p.Trp105Cys, p.Pro129Ser), with a CSF draw indicating abnormal patterns of biogenic amine metabolites, compatible with AADC deficiency. Results After her diagnosis at 3 years of age, medication with levodopa and vitamin B6 failed to show any efficacy. Subsequent administration with a MAO-B inhibitor improved her psychomotor functions to the extent that at 5 years of age she could walk several meters with support. Conclusion Our analyses of chemical findings, together with in silico structure predictions, lead us to hypothesize that this patient retained some AADC activity. In these cases, accurate diagnosis and early treatment should improve patient outcome.