Inborn Errors of Metabolism with Cognitive Impairment Metabolism Defects of Phenylalanine, Homocysteine and Methionine, Purine and Pyrimidine, and Creatine

Phenylketonuria is a defect in phenylalanine metabolism resulting in the excretion of phenylketones and severe intellectual disability. The principle of eliminating the offending amino acid from the diet as a successful treatment strategy was demonstrated. The development of a low-methionine diet to treat homocysteinuria was established after identifying the transsulfuration pathway, resulting in cysteine synthesis. Both conditions are examples of disorders of amino acid metabolism. Lesch-Nyhan syndrome, a rare disorder of purine metabolism resulting in intellectual disability and self injurious behavior, is a classical inborn error of metabolism. Disorders of creatine biosynthesis are relatively newly described and less known diseases.