Karin Kojima1, Rie Anzai2, Chihiro Ohba3, Tomohide Goto2, Akihiko Miyauchi1, Beat Thöny3, Hirotomo Saitsu4, Naomichi Matsumoto5, Hitoshi Osaka6, Takanori Yamagata1. 1. Department of Pediatrics, Jichi Medical University, Japan. 2. Department of Neurology, Kanagawa Children's Medical Center, Japan. 3. Department of Pediatrics, University of Zürich, Switzerland. 4. Department of Human Genetics, Yokohama City University, Graduate School of Medicine, Japan; Department of Biochemistry, Hamamatsu Medical University, Japan. 5. Department of Human Genetics, Yokohama City University, Graduate School of Medicine, Japan. 6. Department of Pediatrics, Jichi Medical University, Japan. Electronic address: hosaka@jichi.ac.jp.
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 3years 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 5years 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.
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 3years 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 5years 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.