title: Aromatic L-amino acid decarboxylase deficiency diagnosed by clinical metabolomic profiling of plasma.
abstract: Aromatic L-amino acid decarboxylase (AADC) deficiency is an inborn error of metabolism affecting the biosynthesis of serotonin, dopamine, and catecholamines. We report a case of AADC deficiency that was detected using the Global MAPS platform. This is a novel platform that allows for parallel clinical testing of hundreds of metabolites in a single plasma specimen. It uses a state-of-the-art mass spectrometry platform, and the resulting spectra are compared against a library of ~2500 metabolites. Our patient is now a 4 year old boy initially seen at 11 months of age for developmental delay and hypotonia. Multiple tests had not yielded a diagnosis until exome sequencing revealed compound heterozygous variants of uncertain significance (VUS), c.286G>A (p.G96R) and c.260C>T (p.P87L) in the DDC gene, causal for AADC deficiency. CSF neurotransmitter analysis confirmed the diagnosis with elevated 3-methoxytyrosine (3-O-methyldopa). Metabolomic profiling was performed on plasma and revealed marked elevation in 3-methoxytyrosine (Z-score +6.1) consistent with the diagnosis of AADC deficiency. These results demonstrate that the Global MAPS platform is able to diagnose AADC deficiency from plasma. In summary, we report a novel and less invasive approach to diagnose AADC deficiency using plasma metabolomic profiling.
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Paldeep S
authors.initials: PS
authors.lastname: Atwal
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Taraka R
authors.initials: TR
authors.lastname: Donti
authors.affiliation: Section of Pediatric Neurology and Neuroscience, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Cardon
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Bacino
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA; Section of Pediatric Neurology and Neuroscience, Baylor College of Medicine, Houston, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Emrick
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: V
authors.initials: V
authors.lastname: Reid Sutton
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA. Electronic address: elsea@bcm.edu.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Elsea
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood*; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000097:blood / Q000172:deficiency*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000097:blood; D004296:Dopa Decarboxylase / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D055432:Metabolomics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D004296:Dopa Decarboxylase; D001142:Aromatic-L-Amino-Acid Decarboxylases; C008404:3-methoxytyrosine
keywords: 3-O-methyldopa; 3-methoxytyrosine; Aromatic l-amino acid decarboxylase deficiency; Metabolomic profiling; Oculogyric crisis