Open AccessPhenylketonuria Pathophysiology: on the Role of Metabolic Alterations
Author(s) -
Patrícia Fernanda Schuck,
Fernanda Malgarin,
José H. Cararo,
Fabíola Cardoso,
Emílio L. Streck,
Gustavo C. Ferreira
Publication year - 2015
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2015.0827
Subject(s) - pathophysiology , medicine , inborn error of metabolism , context (archaeology) , disease , phenylalanine hydroxylase , oxidative stress , phenylalanine , endocrinology , bioinformatics , biochemistry , biology , amino acid , paleontology
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.