Dimensional Measures of Psychopathology in Children and Adolescents Using Large Language Models.

Aromatic ‐amino acid decarboxylase (AADC) deficiency is a life‐threatening and ultrarare (i.e., prevalence <1 per 50 000 persons) disorder of monoamine synthesis, leading essentially to a syndrome that may be conceptualized as “congenital parkinsonism.” AADC deficiency is an autosomal recessive condition caused by biallelic pathogenic variants in the dopa decarboxylase () gene located on chromosome 7, which encodes the aromatic AADC enzyme. The AADC enzyme is important in the synthesis of the neurotransmitters dopamine and serotonin (Figure ). The deficiency causes decreased neurotransmitter levels and severe motor dysfunction. Globally, 123 patients have been reported in the literature, with fewer than 50 currently diagnosed patients in the United States, although rates of misdiagnosis are predicted to be high, especially in high‐risk groups, such as neurological deficits of unknown etiology and cerebral palsy., Recent calculations indicate a birth rate of 44 per year in the United States, with a population prevalence prediction of 840 cases of AADC deficiency in the United States, far lower than the number of currently diagnosed patients. Metabolic pathways of biogenic monoamine neurotransmitters. BH2, quinonoid dihydrobiopterin; BH4, tetrahydrobiopterin; COMT, catechol O‐methyltransferase; ‐DOPA, levodopa; GTP, guanosine triphosphate; GTPCH1, GTP cyclohydroase 1; 5‐HIAA, 5‐hydroxyindoleacetic acid; HVA, homovanillic acid; 5‐HTP, 5 hydroxytryptophan; MAO, monoamine oxidease; MHPG, 3‐methoxy‐4‐hydroxyphenylglycol; VMA, vanillylmandelic acid. There is variable phenotypic severity, with death in the first decade in more severe cases. Roughly 5% of patients are considered “mild” (ambulatory) and 15% “moderate” (nonambulatory, but not bed‐bound), while the remaining 80% of patients are considered severe. Clinical manifestations include hypotonia, oculogyric crises, movement disorders (dystonia, chorea, athetosis), failure to thrive, developmental delay, and autonomic dysfunction.