PHENYLKETONURIA (PKU)

Dr Kumar Ms Jegathambigai1 and Ms Sindhu 1 Biochemistry & Genetics, AIMST University School of Medicine, 08100 Kedah, Malaysia 2 ST Matthews University School of Medicine (SMU), Grand Cayman, Cayman Islands, BWI 3 Department of Biomedical Engineering, Vellore Institute of technology (VIT) Vellore, India
1,2 Ponnusamy 1 RN 3 B

Dr PK_BIOGEN INNO-VISION 2012

Abstract PKU is a inborn error of Phenylalanine (PA) metabolism, the occurrence of PKU varies among ethnic groups and geographic regions worldwide. In the United States, PKU occurs in 1 in 10,000 to 15,000 newborns. Infants with classic PKU are normal at birth but if untreated show slow development, severe mental retardation, autistic symptoms, and loss of motor control. Children may have pale skin and white-blonde hair. The neurotoxic effects relate to high levels of PA and not to the phenylketones (PK) from which the name of the disease derives. Objective: To delineate the molecular and biochemical basis of PKU, diagnosis and management as well to facilitate USMLE preparatory Course: BIOGEN Reusable On-Line Resources for Large Group Teaching-Learning in Relatively Short Time. Molecular-Biochemical Basis of the Disease / Disorder: PKU is a metabolic disease characterizied by accumulation of PA and its by-products in the blood of fetuses and newborns. PKU results from a defect in the enzyme Diffusion-weighted imaging of white Matter abnormalities in patients with PKU Phenylalanine Hydroxylase (PAH), such that PA is not converted to Tyrosine. The alternative Clinical Signs & Symptoms conversion of PA to PPA causes accumulation of the latter as a toxin in the CNS, which can lead to severe mental retardation.

DEFICIENCY
Klung & Cummings 1997 Musty odor, blue eyes, microcephaly & mental Dysmorphic features in maternal PKU retardation

PKU

Bridge to Pharmacology-Toxicology / Management: Diet low

in Phenylalanine, avoid aspartame, diet important during pregnancy. Contraindications: Aspartame (N-aspartyl-phenylalanine methyl ester), which is widely used as an artificial sweetner, must be strictly avoided by Phenylketonurics. Women with PKU who become pregnant must be especially careful about the phenyl alanine level in their blood so as not to adversely affect neuorologic development in the fetus. Infants born to with phenyl ketonuric mothers without metabolic control during pregnency have a high risk of mental retardation, microcephaly and low birth weight. Behavioural Science / Community Medicine / Ethics: PKU Support Society / Genetic counseling-Prenatal Screening in Chorionic Villi Sampling / Referral to PKU Specialty Care Centres.
A Phenylalanine Tyrosine B Homogentisate Valine Maleylacetoacetate Leucine C D Methylmalonyl CoA TCA Cycle E F Acetyl-CoA Glutamate G Alanine Pyruvate

Bridge to Genetics / Inheritance: Autosomal recessive (AR), metabolic genetic disorder, characterized by a mutation in the gene for the hepatic enzyme PAH, rendering it nonfunctional. Laboratory Diagnosis: Infants are routinely screened a few days after birth for blood PA level as well as urinary phenyl pyruvic acid and phenyl acetic acids levels. MCQ: A child with white-blond hair, blue eyes, and pale complexion is on a special diet in which one of the essential amino acids is severely restricted. He has been told to avoid foods artificially sweetened with aspartame. Ans: A. The child has PKU; aspartame contains phenylalanine. These children may be blond, blue Dr PK_BIOGEN INNO-VISION 2012. Doc1 eyed, and pale complected because of deficient References: Kaplan & Google.com melanin production from tyrosine.