Résumé:
Phenylketonuria (PKU) is a metabolic disorder characterized by the body'sinability to properly metabolize phenylalanine (Phe), resulting in its accumulation and subsequentneurological damage. This condition stems from a deficiency in phenylalanine hydroxylase (PAH), the enzyme responsible for converting Phe to tyrosine. The global prevalence of PKU varies around the world withhigher rates in Europe and the United States. PAH activityis essential for maintaining phenylalanine homeostasis and preventinghyperphenylalaninemia, with BH4 serving as a crucial cofactor for PAH function. PKU is an autosomal recessive inborn error of phenylalanine metabolism, primarily caused by mutations in the PAH gene. Hyperphenylalaninemia disruptsbrainfunctionprimarily by competitive lyinhibiting the blood-brainbarrier, leading to deficiencies in criticalbrainaminoacids like tyrosine. This imbalance impairs neurotransmittersynthesis, notably dopamine and serotonin, affecting cognitive and motorfunctions. Advances in PKU care have transformedthroughearlydetection via newborn screening and personalized interventions, including techniques like the Guthrie test and geneticanalysis for precise identification. Treatmentmodalities, including BH4 supplementation and emergingtherapies like PAL enzyme therapy, reflect an evolvinglandscapeencompassingdietaryregulation, large neutral aminoacidsupplementation, enzyme replacement, and genetherapy.
Key Words :
Phenylketonuria, Neurological damage, Phenylalanine hydroxylase, PAH gene mutations, Hyperphenylalaninemia, , Newborn screening, Tetrahydrobiopterin
