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Aromatic L-amino acid decarboxylase deficiency diagnosed by clinical metabolomic profiling of plasma
- Source :
- Europe PubMed Central
- Publication Year :
- 2015
-
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.
- Subjects :
- Male
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Compound heterozygosity
Biochemistry
Polymorphism, Single Nucleotide
chemistry.chemical_compound
Endocrinology
Internal medicine
Genetics
medicine
Humans
Metabolomics
Molecular Biology
Amino Acid Metabolism, Inborn Errors
Exome sequencing
5-Hydroxyindoleacetic acid
Homovanillic acid
Infant
medicine.disease
Hypotonia
Dihydroxyphenylalanine
chemistry
Inborn error of metabolism
Aromatic-L-Amino-Acid Decarboxylases
Dopa Decarboxylase
Tyrosine
medicine.symptom
5-Hydroxytryptophan
3-O-Methyldopa
medicine.drug
Subjects
Details
- ISSN :
- 10967206
- Volume :
- 115
- Issue :
- 2-3
- Database :
- OpenAIRE
- Journal :
- Molecular genetics and metabolism
- Accession number :
- edsair.doi.dedup.....f1c7689648a0345aeef997dc1bcc1daf