Prevalence of Aromatic l-Amino Acid Decarboxylase Deficiency in At-Risk Populations

• Published in: Pediatric neurology Vol. 106; pp. 38 - 42
• Main Authors: Hyland, Keith, Reott, Michael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2020
• Subjects: Adult; Amino acid metabolism; Amino Acid Metabolism, Inborn Errors - diagnosis; Amino Acid Metabolism, Inborn Errors - epidemiology; Amino Acid Metabolism, Inborn Errors - genetics; Amino Acid Metabolism, Inborn Errors - metabolism; Aromatic l-amino acid decarboxylase; Aromatic-L-Amino-Acid Decarboxylases - deficiency; Aromatic-L-Amino-Acid Decarboxylases - genetics; Aromatic-L-Amino-Acid Decarboxylases - metabolism; Child; Child, Preschool; Disease Susceptibility; Dopa decarboxylase; Dopamine; Dopamine - metabolism; Female; Humans; Inborn errors; Infant; Male; Neurotransmitters; Prevalence; Retrospective Studies; Risk; Sequence Analysis, DNA; United States; Young Adult; United States; Inborn errors; Aromatic l-amino acid decarboxylase; Neurotransmitters; Dopamine; Dopa decarboxylase; Amino acid metabolism
• ISSN: 0887-8994; 1873-5150
• DOI: 10.1016/j.pediatrneurol.2019.11.022

Aromatic l-amino acid decarboxylase (AADC) deficiency is an autosomal recessive metabolic disorder that results from disease-causing pathogenic variants of the dopa decarboxylase (DDC) gene. Loss of dopamine and serotonin production in the brain from infancy prevents achievement of motor developmental milestones.
We retrospectively evaluated data obtained from requests to Medical Neurogenetics Laboratories for analyses of neurotransmitter metabolites in the cerebrospinal fluid, AADC enzyme activity in plasma, and/or Sanger sequencing of the DDC gene. Our primary objective was to estimate the prevalence of AADC deficiency in an at-risk population.
Approximately 20,000 cerebrospinal fluid samples were received with a request for neurotransmitter metabolite analysis in the eight-year study period; 22 samples tested positive for AADC deficiency based on decreased concentrations of 5-hydroxyindoleacetic acid and homovanillic acid, and increased 3-O-methyldopa, establishing an estimated prevalence of approximately 0.112%, or 1:900. Of the 81 requests received for plasma AADC enzyme analysis, 25 samples had very low plasma AADC activity consistent with AADC deficiency, resulting in identification of nine additional cases. A total of five additional patients were identified by Sanger sequencing as the primary request leading to the diagnosis of AADC deficiency.
Overall, these analyses identified 36 new cases of AADC deficiency. Sequencing findings showed substantial diversity with identification of 26 different DDC gene variants; five had not previously been associated with AADC deficiency. The results of the present study align with the emerging literature and understanding of the epidemiology and genetics of AADC deficiency.