Phenylalanine–tyrosine–catecholamine axis disorders: pathways, molecular diagnosis, therapeutics, and emerging translational monitoring technologies

Disorders of the phenylalanine–tyrosine–catecholamine axis are a clinically relevant group of neurometabolic conditions in which pathogenic variants in key enzymes impair dopamine and norepinephrine biosynthesis. Patients may present with movement disorders, autonomic dysfunction, developmental delay, and related neurobehavioral manifestations. In this narrative review, we synthesize the main enzymatic defects across the axis, focusing on phenylalanine hydroxylase, tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and dopamine beta-hydroxylase. We describe how diagnostic practice has evolved from isolated biochemical assays to integrated approaches that link clinical phenotyping with targeted biochemical profiling and molecular confirmation. Genetic testing now supports diagnosis, treatment planning, and family counseling, while chromatographic and mass spectrometry-based methods remain essential for quantifying amino acids and neurotransmitter-related metabolites. We also discuss emerging biosensor-based strategies as a potential route to decentralized and minimally invasive monitoring.