Aromatic L-Amino Acid Decarboxylase Deficiency: A Genetic Screening in Sicilian Patients with Neurological Disorders

• Published in: Genes 2024-01, Vol.15 (1), p.134
• Main Authors: Santa Paola, Sandro, Di Blasi, Francesco Domenico, Borgione, Eugenia, Lo Giudice, Mariangela, Giuliano, Marika, Pettinato, Rosa, Di Stefano, Vincenzo, Brighina, Filippo, Lupica, Antonino, Scuderi, Carmela
• Format: Article
• Language: English
• Subjects: Amino Acid Metabolism, Inborn Errors; Amino acids; Aromatic-L-amino-acid decarboxylase; Aromatic-L-Amino-Acid Decarboxylases - genetics; Autism; Autism Spectrum Disorder - genetics; Autonomic nervous system; Behavior disorders; Biosynthesis; Cerebrospinal fluid; Child development; Cognition disorders; Cognitive ability; Cystic fibrosis; Diagnostic tests; Disease; Dopamine; Dystonia; Enzymes; Gene therapy; Genetic screening; Genetic Testing; Genotype & phenotype; Hereditary diseases; Humans; Infant, Newborn; Intellectual disabilities; Medical research; Medical screening; Medicine, Experimental; Metabolic disorders; Mitochondrial DNA; Movement disorders; Nervous system diseases; Nervous System Diseases - genetics; Neurological diseases; Neurological disorders; Neuromuscular diseases; Norepinephrine; Patients; Phenylketonuria; Physiological aspects; Proteins; Serotonin; Spinal muscular atrophy
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes15010134

Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare autosomal recessive neurometabolic disorder caused by AADC deficiency, an enzyme encoded by the gene. Since the enzyme is involved in the biosynthesis of serotonin and dopamine, its deficiency determines the lack of these neurotransmitters, but also of norepinephrine and epinephrine. Onset is early and the key signs are hypotonia, movement disorders (oculogyric crises, dystonia and hypokinesia), developmental delay and autonomic dysfunction. Taiwan is the site of a potential founder variant (IVS6+4A>T) with a predicted incidence of 1/32,000 births, while only 261 patients with this deficit have been described worldwide. Actually, the number of affected persons could be greater, given that the spectrum of clinical manifestations is broad and still little known. In our study we selected 350 unrelated patients presenting with different neurological disorders including heterogeneous neuromuscular disorders, cognitive deficit, behavioral disorders and autism spectrum disorder, for which the underlying etiology had not yet been identified. Molecular investigation of the gene was carried out with the aim of identifying affected patients and/or carriers. Our study shows a high frequency of carriers (2.57%) in Sicilian subjects with neurological deficits, with a higher concentration in northern and eastern Sicily. Assuming these data as representative of the general Sicilian population, the risk may be comparable to some rare diseases included in the newborn screening programs such as spinal muscular atrophy, cystic fibrosis and phenylketonuria.