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

详细信息    查看全文

• 作者：Karin Kojima^a ; ¹ ; Rie Anzai^b ; ¹ ; Chihiro Ohba^c ; Tomohide Goto^b ; Akihiko Miyauchi^a ; Beat Thö ; ny^c ; Hirotomo Saitsu^d ; ^e ; Naomichi Matsumoto^d ; Hitoshi Osaka^a ; ^{hosaka@jichi.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Takanori Yamagata^a
• 关键词：Aromatic l amino acid decarboxylase (AADC) deficiency ; Whole exome sequencing ; MAO-B inhibitor ; 3-O-methyl-l-dopa (3-OMD)
• 刊名：Brain and Development
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：38
• 期：10
• 页码：959-963
• 全文大小：784 K

文摘

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.