PHENYLKETONURIA:

PHENYLKETONURIA:

·     Phenylketonuria is an inherited error of metabolism caused by a deficiency in the enzyme phenylalanine hydroxylase (PAH). Loss of this enzyme results in mental retardation, organ damage, unusual posture and can, in cases of maternal PKU, severely comprise pregnancy.

·     Classical PKU is an autosomal recessive disorder, caused by mutation in both alleles of the gene for PAH, found on chromosome 12. In the body, PAH converts the amino acid phenylalanine to tyrosine, another Amino acid. Mutation in both copies of Gene for PAH means that the enzyme is inactive or less efficient, and the concentration of phenylalanine in the body can build up to toxic levels.

·     In some cases, mutations in PAH will result in a phenotypically mild form of PKU called hyperphenylalaninemia.

·     PKU is a classic ‘monogenic’ autosomal recessive disease in which mutation in the human PAH locus explain the impaired function of enzyme PAH, the attendant hyperphenylalaninemia (metabolic phenotype) and the resultant mental retardation (cognitive phenotype).

·     Tyrosine is needed to create neurotransmitter such as epinephrine, norepinephrine and dopamine.

·     Symptoms :

·     (a) seizures, tremors (shaking)

·     (b) stunted growth.

·      (c) mental retardation.

·     (d) intellectual disability

·     (e) hypopigmentation (excessively fair skin and hair)

·     (f) 'musty odor’ to the baby's sweat and urine (due to phenylacetate, a carboxylic acid produced by the oxidation of phenyl ketone).

·     (g) phenylpyruvate can be detected in urine.

·     Phenylalanine is a large neutral amino acid (LNAA). It competes for transport across blood- brain barrier via the transporter. In excess it saturate the transporter, decreasing the levels of other LNAA in brain. This hinders the development of brain.

·     Treatment:  (a) restricted diet (eliminating food rich in phe. Like eggwhite, chicken, legumes, fish, soybeans, cheese)

·     (B) oral administration of tetrahydrobiopterin.

·      (c) casein glycomacropeptide (cGMP), milk peptide naturally free of phe.

·     Detection : newborn screening.