Histopathological Effects on the Eye Development during Perinatal Growth of Albino Rats Maternally Treated with Experimental Phenylketonuria during Pregnancy

  • Mahmoud E. Mohallal Zoology Department, Faculty of Science, Suez Canal University, Egypt.
  • Hany A. Hefty Zoology Department, Faculty of Science, Suez Canal University, Egypt.
  • Hassan I. Elsayyad Zoology Department, Faculty of Science, EL Mansoura University, Egypt.
  • Hala M. Ebied Zoology Department, Faculty of Science, Suez Canal University, Egypt.
Keywords: PKU, Eye, Perinatal, Rat


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.


Download data is not yet available.


[1]. Fölling, A. (1934). Über Ausscheidung von Phenylbrenztraubensäure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillität. Hoppe Seylers Z. Physiol. Chem., 227:169—176.
[2]. Pietz, J. (1998). Neurological aspects of adult phenylketonuria. Curr. Opin. Neurol., 11: 679–88.
[3]. Roberts, S.A., Thorpe, J.M., Ball, R.O. and Pencharz, P.B. (2001). Tyrosine requirement of healthy men receiving a fixed phenylalanine intake determined by using indicator amino acid oxidation. Am. J. Clin. Nutr., 73(2):276-82.
[4]. Tam, S.Y. and Roth, R.H. (1997). Mesoprefrontal dopaminergic neurons: can tyrosine availability influence their functions? Biochem. Pharmacol., 53(4):441-53.
[5]. Recommendations on the dietary management of phenylketonuria. Report of Medical Research Council Working Party on Phenylketonuria (1993). Archives of Disease in Childhood, 68(3), 426-7.
[6]. Kaufman, S., Kapatos, G., Rizzo, W.B., Schulman, J.D., Tamarkin, L., Van Loon, G.R. (1983). Tetrahydropterin therapy for hyperphenylalaninemia caused by defective synthesis of tetrahydrobiopterin. Ann. Neurol., 14(3): 308-15.
[7]. Robson, K.J., Chandra, T., MacGillivray, R.T., Woo, S.L. (1982). Polysome immunoprecipitation of phenylalanine hydroxylase mRNA from rat liver and cloning of its cDNA. Proc. Natl. Acad. Sci. USA, 79: 4701-4705.
[8]. Zschocke, J. (2003). Phenylketonuria mutations in Europe. Hum. Mutat., 21(4):345-56.
[9]. Scriver, C.R., Hurtubise, M., Konecki, D., Phommarinh, M., Prevost, L., Erlandsen, H., Stevens, R., Waters, P.J., Ryan, S., McDonald, D., Sarkissian, C. (2003). PAHdb 2003: what a locus-specific knowledgebase can do. Hum. Mutat., 21:333-44.
[10]. Brenton, D.P. and Lilburn, M. (1996). Maternal phenylketonuria. A study from the United Kingdom. Eur. J. Pediatr., 155 Suppl 1:S177-80.
[11]. Koch, R., Hanley, W., Levy, H., Matalon, R., Rouse, B., Trefz, F., Guttler, F., Azen, C., Friedman, E., Platt, L., de la Cruz, F. (2000). Maternal phenylketonuria: An international study. Mol. Genet. Metab., 71(1-2):233-9.
[12]. Rouse, B., Azen, C., Koch, R., Matalon, R., Hanley, W., de la Cruz, F., Trefz, F., Friedman, E., Shifrin, H. (1997). Maternal Phenylketonuria Collaborative Study (MPKUCS) offspring: facial anomalies, malformations, and early neurological sequelae. Am. J. Med. Genet., 69(1): 89-95.
[13]. Rohr, F.J., Lobbregt, D. and Levy, H.L. (1998). Tyrosine supplementation in the treatment of Maternal Phenylketonuria. Am. J. Clin. Nutr., 67: 473-6.
[14]. Pietz, J., Dunckelmann, R., Rupp, A., Rating, D., Meinck, H.M., Schmidt, H., Bremer, H.J. (1998). Neurological outcome in adult patients with early-treated Phenylketonuria. Eur. J. Pediatr., 157(10):824-30.
[15]. Williams, K. (1998). Benefits of normalizing plasma phenylalanine: impact on behavior and health. A case report. J. Inherit. Metab. Dis., 21: 785-90.
[16]. Christen, S.D., Hill, T.M., Williams, M.S. (1996). Effects of tempered barley on milk yield, intake, and digestion kinetics of lactating Holstein cows. J. Dairy Sci., 79: 1394-1399.
[17]. Rech, V.C., Feksa, L.R., Dutra-Filho, C.S., Wyse, A.T., Wajner, M. and Wannmacher, C.M. (2002). Inhibition of the mitochondrial respiratory chain by phenylalanine in rat cerebral cortex. Neurochem. Res., 27: 353–357.
[18]. Drury, R.A. and Wallington, E.A. (1980). Carleton's Histological Technique. 5th Edition, Oxford University Press, New York.
[19]. Field, A.P. (2000). Discovering statistics using SPSS for Windows: Advanced techniques for the beginner. London: Sage Publications.
[20]. Jervis, G.A., Block, R.J., Bolling, D. and Kanze, E. (1940). Chemical and Metabolic Studies on Phenylalanine. II. The Phenylalanine Content of the Blood and Spinal Fluid in Phenylpyruvic Oligophrenia. J. Biol. Chem., 134: 105-113.
[21]. Jervis, G.A. (1953). Phenylpyruvic oligophrenia deficiency of phenylalanine-oxidizing system. Proc. Soc. Exp. Biol. Med., 82: 514-515.
[22]. Scriver, C.R. and Kaufman, S. (2001). Hyperphenylalaninemia: phenylalanine hydroxylase deficiency. In: Scriver, C.R., Beaudet, A.L., Sly, S.W., Valle, D., eds; Childs, B., Kinzler, K.W., Vogelstein, B. assoc eds. The Metabolic and Molecular Bases of Inherited Disease. 8 ed. New York, NY: McGraw-Hill; 1667-724.
[23]. Diamond, A. (1996). Evidence for the importance of dopamine for prefrontal cortex functions early in life. Philos. Trans. R. Soc. Lond. B. Biol. Sci., 351(1346):1483-93.
[24]. Wurtman, R.J. and Wurtman, J.J. (1979). Toxic effects of food constituents on the brain. In: Guroff, G. (ed.). Nutrition and the Brain, Vol. 4. New York: Raven Press, 29–78.
[25]. Gazit, V., Ben-Abraham, R., Pick, C.G., Katz, Y. (2003). beta-Phenylpyruvate induces long-term neurobehavioral damage and brain necrosis in neonatal mice. Behav. Brain Res., 143(1):1-5.
[26]. Jervis, G.A. (1939). The Genetics of Phenylpyruvic Oligophrenia: A Contribution to the Study of the Influence of Heredity on Mental Defect. Journal of Mental Science, (85): 719-762.
[27]. Fisch, R.O., Matalon, R., Weisberg, S., Michals, K. (1991). Children of fathers with phenylketonuria: An international survey. J. Pediatr., 118: 739-741.
[28]. Gardiner, R.M. (1990). Transport of amino acids across the blood-brain barrier: Implications for treatment of maternal phenylketonuria. J. Inherit. Metab. Dis., 13: 627-33.
[29]. Schoonheyta, W.E., Clarkea, J.T.R., Hanley, W.B., Johnsonb, J.M., Lehotay, D.C. (1994). Feto-maternal plasma phenylalanine concentration gradient from 19 weeks gestation to term. Clinica Chimica Acta, 225(2): 165-169.
[30]. Austic, R.E. and Grau, C.R. (1971). Degeneration of the eyes and central nervous system of chick embryos subjected to phenylalanine or tyrosine deficiency. Dev. Biol., 25: 159-175.
[31]. Andersen, A.E., Rowe, V. and Guroff, G. (1974). The Enduring Behavioral Changes in Rats with Experimental Phenylketonuria. Proc. Natl. Acad. Sci., 71(1): 21-5.
[32]. Wen, G.Y., Wisniewski, H.M., Shek, J.W., Loo, Y.H., Fulton, T.R. (1980). Neuropathology of phenylacetate poisoning in rats: an experimental model of Phenylketonuria. Ann. Neurol.; 7(6): 557-66.
[33]. Diamond, A. and Herzberg, C. (1996). Impaired sensitivity to visual contrast in children treated early and continuously for PKU. Brain, 119 (Pt 2): 523-38.
[34]. Agostoni, C., Massetto, N., Biasucci, G., Rottoli, A., Bonvissuto, M., Bruzzese, M.G., Giovannini, M., Riva, E. (2000). Effects of long-chain polyunsaturated fatty acid supplementation on fatty acid status and visual function in treated children with hyperphenylalaninemia. J. Pediatr., 137: 504-509.
How to Cite
Mohallal, M., Hefty, H., Elsayyad, H., & Ebied, H. (2016). Histopathological Effects on the Eye Development during Perinatal Growth of Albino Rats Maternally Treated with Experimental Phenylketonuria during Pregnancy. Journal of Advanced Laboratory Research in Biology, 7(2), 36-42. Retrieved from https://e-journal.sospublication.co.in/index.php/jalrb/article/view/247