title: Unusually mild phenotype of AADC deficiency in 2 siblings.
abstract: Aromatic L-amino acid decarboxylase deficiency is a rare neurotransmitter defect leading to serotonin, dopamine and norepinephrine deficiency. Affected individuals usually present in infancy with severe developmental delay, oculogyric crises and extrapyramidal movements. We present the clinical, molecular and biochemical features of a pair of siblings who presented with fatigability, hypersomnolence and dystonia and who showed excellent response to treatment. Analysis of CSF biogenic amines, plasma AADC levels and direct sequencing of the DDC gene was performed. CSF catecholamine metabolites were reduced, with elevation of 3-O-methyldopa. Plasma AADC activity was undetectable in both siblings, and decreased in their carrier parents. One missense mutation (853C>T) was found in exon 8, and a donor splice site mutation was found in the intron after exon 6 (IVS6+4A>T). Both siblings showed excellent response to MAO inhibitor and dopamine agonist treatment. This report expands the clinical spectrum of AADC deficiency and contributes to the knowledge of the genotype and phenotype correlation for the DDC gene. It is important to recognize the milder phenotypes of the disease as these patients might respond well to therapy.
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore. stacey@nus.edu.sg
authors.forename: S K H
authors.initials: SK
authors.lastname: Tay
authors.forename: K S
authors.initials: KS
authors.lastname: Poh
authors.forename: K
authors.initials: K
authors.lastname: Hyland
authors.forename: Y W
authors.initials: YW
authors.lastname: Pang
authors.forename: H T
authors.initials: HT
authors.lastname: Ong
authors.forename: P S
authors.initials: PS
authors.lastname: Low
authors.forename: D L M
authors.initials: DL
authors.lastname: Goh
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001034:Apgar Score; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000172:deficiency* / Q000235:genetics*; D001679:Biogenic Amines / Q000134:cerebrospinal fluid; D002395:Catecholamines / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype; D035781:Siblings
chemical_list: D001679:Biogenic Amines; D002395:Catecholamines; D001142:Aromatic-L-Amino-Acid Decarboxylases