*Corresponding author: E-mail: hanyhefny56@yahoo.com. Journal of Advanced Laboratory Research in Biology E-ISSN: 0976-7614 Volume 7, Issue 2, 2016 PP 36-42 https:/ / e-journal.sospublication.co.in Research Article Histopathological Effects on the Eye Development during Perinatal Growth of Albino Rats Maternally Treated with Experimental Phenylketonuria during Pregnancy Mahmoud E. Mohallal 1 , Hany A. Hefty 1,3* , Hassan I. Elsayyad 2 & Hala M. Ebied 1 1 Zoology Department, Faculty of Science, Suez Canal University, Egypt. 2 Zoology Department, Faculty of Science, EL Mansoura University, Egypt. 3 Biology Department, University College, Umm Al-Qura University Al-Jomoum, KSA. Abstract: Phenylketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. The disease results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine to tyrosine. Although, this inborn error of metabolism was among the first in humans to be understood biochemically and genetically, little is known about the mechanisms involved in the pathology of PKU during neonatal brain development. Elevated concentrations of plasma phenylalanine were induced in pregnant rats by oral administration of 50mg/100g body weight alpha- methylphenylalanine plus phenylalanine supplementation at a dosage of 60mg/100g body weight two times daily after 6th day of onset of gestation till 14 & 16 days prenatal as well as at parturition. Treatment with alpha- methylphenylalanine resulted in significant reduction of retinal cell layers of prenatal fetuses and delivered newborns. Histological abnormalities were detected manifested by either hyaline degeneration of lens structure or inducing lens cataract as well as comparative atrophy of retina associated with the development of malignant polypoid mass in the ganglionic cell layers in contact with the lens. Keywords: PKU; Eye; Perinatal; Rat. 1. Introduction Phenylketonuria (PKU) disease was first described in 1934 by a Norwegian doctor named Asbjörn Fölling [1]. He concluded that the disorder of phenylalanine metabolism was the cause of the children’s mental retardation and gave the name Phenylketonuria to this condition. Subsequent examinations of PKU patients excreting phenylpyruvic acid proved that phenylalanine was accumulated in their bodies. In Phenylketonuria, phenylalanine accumulates in the blood as the result of a deficiency or malfunction of the liver enzyme phenylalanine hydroxylase (PAH), which under normal conditions converts phenylalanine to L-tyrosine [2]. Consequently, individuals with PKU are low in L-tyrosine [3] which may contribute to behavior problems [4]. Phenylalanine is one of the building blocks of protein. It is found in protein when the phenylalanine hydroxylase enzyme is absent or deficient, phenylalanine abnormally accumulates in the blood. Inability to remove excess phenylalanine from the blood during infancy and early childhood produces a variety of problems including mental retardation. Universal newborn screening can identify genetic defects and these problems can be greatly reduced by placing the child on a special diet within the first few days of life [5]. The most common cause for a lack of this enzyme is a genetic defect in the gene for PAH, where most patients suffering from PKU have one or another of several possible mutations in this gene, and PAH activity is a defect in the generation of adequate amounts of the cofactor tetrahydrobiopterin (BH 4 ). BH 4 is an essential coenzyme not only for the hydroxylation of phenylalanine to tyrosine but also for the hydroxylation of tyrosine to L-dopa required for dopamine biosynthesis and for the hydroxylation of tryptophan to 5-hydroxytryptophan, the substrate for