Phenylketonuria Essay

Introduction
Phenylketonuria (PKU) is a rare congenital autosomal recessive condition that is caused by an error in amino acid metabolism. Due to a mutation in the phenylalanine hydroxylase (PAH) gene, the body is unable to hydrolyse excessive quantities of phenylalanine (Phe) leading to toxic concentrations in the brain. Under the action of PAH together with co-factor tetrahydrobiopterin (BH4), iron and oxygen, phenylalanine is converted to tyrosine (Tyr). Sufferers of PKU often face developmental problems, intellectual deficiency and abnormal behaviour (1). On an epidemiological note, occurrence of PKU is highest amongst Caucasians with incidence of 1 in 10,000 births (2). The highest rate of occurrence is in Turkey occurring at 1 in 2,600 …show more content…
Such a study carried out by Nagasaka and colleagues (4) showed that PKU causes the down-regulation of an enzyme (3-hydroxy-3-methylglutaryl coenzyme A reductase) responsible for cholesterogenesis. As a result, the total serum lipoprotein level is significantly lowered. This is associated with hypomyelination where myelin sheath synthesis is disrupted causing neural damage - symptomatically characterised by slow speech and communication exhibited by …show more content…
This is because there is a high affinity between Phe and Large Neutral Amino Acid (LNAA) transporter, thus competing with other LNAAs such as Tyr and Tryptophan (Trp) from crossing the Blood-Brain Barrier (BBB). Furthermore, Phe is a competitive inhibitor of enzymes Tyr hydroxylase and Trp hydroxylase. These enzymes together with Tyr and Trp are required for neurotransmitter synthesis especially serotonin and dopamine (5). Neurobehavioural symptoms such as hyperactivity, lethargy, moodiness and depression are hallmarks of deficient neurotransmitter metabolism due to lack of serotonin and dopamine (3).
Some studies have shown that there is a negative correlation between plasma concentration of Phe and cerebral protein synthesis. Primarily this is thought to be due to LNAA transport of Phe across BBB preventing Trp and Tyr entering the brain but also due to lack of methionine incorporation into proteins during intiation (6). All in all, the 3 primary metabolic alterations are responsible for cognitive symptoms, however there are many more as discussed below.
Symptoms and

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