Phenylketonuria: Genes in phenylketonuria, diagnosis, and treatments

Abstract

Introduction: Phenylketonuria (PKU) is a rare autosomal-recessive disorder inherited in accordance with the law of segregation. Detection tools for people with PKU can include Sanger Sequencing (SS) and Next Generation Sequencing (NGS). Diet therapy, Large Neutral Amino Acids (LNAA), and Specific Nutrient Combination (SNC) can help alleviate people with PKU. In the future, genetic manipulation techniques can help to eliminate PKU. Objectives: In this review, the author describes the progress in a study that focused on detection tools such as SS and NGS, the phenylalanine hydroxylase (PAH) gene and mutations in the PAH gene, use of drugs for PKU, and genetic manipulation techniques such as Adeno-associated virus (AAV) vectors and clustered regularly interspaced short palindromic repeats (CRISPR) RNA-guided FokI nuclease system (FokI-dCas9 system). AAV is abbreviation of AAV. CRISPR system is abbreviation of clustered regularly interspaced short palindromic repeats. Methods: The author searched the PubMed Database at National Center for Biotechnology Information (NCBI) for articles on PKU disorder. These articles were published between 2014 and 2019. Articles were open access and in English. Searches were also done at Google and ScienceDirect. Results: PKU derives from mutations in the PAH gene. Features of PKU may include ataxia, intellectual ability, and seizures. MassARRAY method, minisequencing method, SS and NGS can detect PKU on humans. Diet therapy, BH 4 , LNAA, SNC, enzyme therapy can help patients with PKU. However, these drugs cannot treat PKU permanently. In the future, genetic manipulation techniques can be used. AAV vectors and FokI-dCas9 system can be useful to eliminate PKU disorder. Conclusion: Guthrie method, MassARRAY, minisequencing, SS and NGS are tools for detecting PKU. Treatments with such as diet therapy, LNAA, SNC, and enzyme therapy are useful for PKU disorder. AAV vectors and FokI-dCas9 system are methods that can be useful for eliminating PKU in the future.

Mutation Characteristics of Phenylalanine Hydroxylase Gene in Children with Phenylketonuria in Yinchuan City

“…Untreated individuals may experience severe intellectual disability, seizures, behavioral and psychiatric issues, motor problems, as well as characteristic physical features such as fair skin, light-colored eyes and hair, eczema, and a moldy odor [2]. Despite being the most common amino acid metabolism disorder, the underlying mechanisms of brain dysfunction in patients with PKU remain poorly understood, warranting further research to facilitate the development of pathophysiology-driven therapies [10,11].…”