title: Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations.
abstract: Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism caused by the deficiency of phenylalanine hydroxylase. This deficiency leads to the accumulation of Phe and its metabolites in tissues and body fluids of PKU patients. The main signs and symptoms are found in the brain but the pathophysiology of this disease is not well understood. In this context, metabolic alterations such as oxidative stress, mitochondrial dysfunction, and impaired protein and neurotransmitters synthesis have been described both in animal models and patients. This review aims to discuss the main metabolic disturbances reported in PKU and relate them with the pathophysiology of this disease. The elucidation of the pathophysiology of brain damage found in PKU patients will help to develop better therapeutic strategies to improve quality of life of patients affected by this condition.
authors.affiliation: 1 Laboratório de Erros Inatos do Metabolismo, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Patrícia Fernanda
authors.initials: PF
authors.lastname: Schuck
authors.affiliation: 1 Laboratório de Erros Inatos do Metabolismo, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Malgarin
authors.affiliation: 1 Laboratório de Erros Inatos do Metabolismo, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: José Henrique
authors.initials: JH
authors.lastname: Cararo
authors.affiliation: 2 Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Cardoso
authors.affiliation: 3 Laboratório de Bioenergética, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Emilio Luiz
authors.initials: EL
authors.lastname: Streck
authors.affiliation: 2 Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Gustavo Costa
authors.initials: GC
authors.lastname: Ferreira
keywords: brain; hyperphenylalaninemia; metabolic alterations; phenylalanine; phenylketonuria