Fenilcetonúria - Importância do diagnóstico e tratamento

Abstract

Phenylketonuria (PKU) is an autosomal recessive genetic disease caused by mutations in the PAH gene (phenylalanine hydroxylase enzyme), which leads to the accumulation of phenylalanine in the blood and tissues, resulting in neurotoxic effects that compromise cognitive and motor development. Since its discovery in 1934 by Asbjørn Fölling, PKU has undergone significant diagnostic and therapeutic advances, justifying the need to update these aspects through a narrative literature review of databases from PubMed, Google Scholar, and SciELO. Neonatal screening, performed through the heel prick test, is the primary method for early detection of the disease, enabling treatment before clinical manifestations. In Brazil, the National Neonatal Screening Program achieves broad coverage, although regional inequalities persist. With advances in biotechnology, next-generation sequencing (NGS) has become a promising tool, capable of identifying specific genetic variants and expanding the diagnosis of inherited metabolic diseases. Treatment is primarily based on dietary phenylalanine restriction and the use of special metabolic formulas, and can be complemented by pharmacological therapies such as sapropterin (BH₄) and pegvaliase, approved for specific cases. Recent studies are also investigating innovative alternatives, such as the use of genetically modified probiotics (SYNB1618) and CRISPR/Cas9 gene therapies, still in the experimental phase. Therefore, early neonatal screening, continuous monitoring, and multidisciplinary management are essential to ensure healthy development and prevent irreversible consequences caused by phenylketonuria.