Unusually mild phenotype of AADC deficiency in 2 siblings

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, mol...

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Bibliographic Details
Published in:Molecular genetics and metabolism 2007-08, Vol.91 (4), p.374-378
Main Authors: Tay, S.K.H., Poh, K.S., Hyland, K., Pang, Y.W., Ong, H.T., Low, P.S., Goh, D.L.M.
Format: Article
Language:English
Subjects:
AADC deficiency
Amino Acid Sequence
Amino Acid Substitution
Apgar Score
Aromatic l-amino acid decarboxylase deficiency
Aromatic-L-Amino-Acid Decarboxylases - deficiency
Aromatic-L-Amino-Acid Decarboxylases - genetics
Biogenic amines
Biogenic Amines - cerebrospinal fluid
Catecholamines - cerebrospinal fluid
DDC gene
Dystonia
Female
Humans
Infant
Molecular Sequence Data
Mutation, Missense
Phenotype
Siblings
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Summary: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.
ISSN:1096-7192
1096-7206
DOI:10.1016/j.ymgme.2007.04.006