Emerging biosensors in Phenylketonuria

Abstract

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder resulting from deficient phenylalanine hydroxylase (PAH) enzyme activity, leading to impaired phenylalanine (Phe) metabolism. This condition can lead to intellectual disability, epilepsy, and behavioural issues. Treatment typically involves strict dietary restrictions on natural protein intake, supplemented with chemically manufactured protein substitutes containing amino acids other than Phe. Various approaches, including casein glycomacropeptide (GMP), tetrahydrobiopterin (BH₄), phenylalanine ammonia-lyase (PAL) therapy, large neutral amino acid (LNAA) supplementation, enzyme therapy, gene therapy, and medical therapies, aim to prevent Phe transport in the brain to potentially treat PKU. Although newborn screening programs and early dietary interventions have enhanced outcomes of the potential treatment strategies, limitations still persist in this direction. These involve potent accuracy concerns in diagnosis due to the existence of antibiotics in blood of PKU patients, affecting growth of the bacteria in the bacterial inhibition assay. Monitoring involves complex methods for instance, mass spectrometry and high-pressure liquid chromatography, which involve shortcomings such as lengthy protocols and the need for specialized equipment. To address these limitations, adaptable testing formats like bio/nano sensors are emerging with their cost-effectiveness, biodegradability, and rapid, accurate, and sensitive detection capabilities, offering promising alternatives for PKU diagnosis. This review provides insights into current treatment and diagnostic approaches, emphasizing on the potential applications of the diverse sensors intended for PKU diagnosis.

Keywords: Diagnosis; Hyperphenylalaninemia; Phenylalanine; Phenylalanine hydroxylase; Phenylketonuria; Sensors.