Abstract

PHENYLKETONURIA: AN OVERVIEW OF PATHOPHYSIOLOGY, DIAGNOSIS, AND MANAGEMENT

Komalba Sarvaiya, Sapna Desai*, Satyajit Sahoo, Rashmi Rajeghorpade, Archana Kaushik, Tejas Patel, D. B. Meshram

ABSTRACT

Phenylketonuria is an autosomal inborn error of metabolism characterized predominantly by dysfunctional phenylalanine (L-alpha-amino-beta-phenylpropionic acid) metabolism due to defects in phenylalanine hydroxylase (PAH) activity. Because of elevated levels of phenylalanine and low levels of tyrosine, neurologial symptoms and other system effects are produced. PKU has a variable worldwide prevalence that is modulated by ethnicity and geographic region. This disorder is usually linked with a destructive mutation in the PAH gene, while hyperphenylalaninemia may also result from an error in tetrahydrobiopterin (BH₄) metabolism. Elevated phenylalanine and its products can influence the central nervous system by acting as inhibitors of the large neutral amino acids transporter 1 (LAT1), altering neurotransmitters availability, compromising protein synthesis in the brain and generating oxidative stress. PKU may lead to severe intellectual disability, such as behavioral problems, seizures, microcephaly, hypopigmentation, as well as musty odour. A mothers' PKU may also have the opportunity to cause high risk of negative fetal outcomes with such possibilities of having microcephaly, disability, intelligence disability, growth retardation and even congenital heart defects. Identification with the help of newborn screening method with biochemical confirmation, and BH4 disorder evaluation is crucial for appropriate management. The main treatment for PKU will remain dietary phenylalanine restriction supported by medical formula and other amino acid supplements. Sapropterin and pegvaliase are included in pharmacological approaches, whereas gene therapy, enzyme therapy, microbial therapy, mRNA therapy, and red cell therapy serve as novel medical plans. Comprehensive Management and Early Diagnosis of phenylalanine level is very essential to decrease the risks related to this disease.

Keywords: Phenylketonuria (PKU), PAH gene, Tetrahydrobiopterin (BH4), LAT1, Sapropterin, Pegvaliase.