Sandbox Reserved 768: Difference between revisions

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== Phenylketonuria ==

~~Dysfunctional PAH consequently prevents the conversion of L-phenylalanine into L-tyrosin. This leads to the accumulation of phenylalanine in the blood. This subsequent increase in the concentration~~

'''Overview'''

Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. <ref name="lendly"> Lendley, Fred, Anthony DeLilla, and Savio Woo. "Molecular Biology of Phenylalanine Hydroxylase and Phenylketonuria." Trends in Genetics 1(1985): 309-313. Web.</ref>. It is genetic autosomal recessive disorder and a relatively common condition affecting approximately 1 in 10,000 newborn infants in the USA and Europe. <ref name="lendly"/>. The Phenylhydroxylase enzyme gene consists of 13 exons and introns and when both alleles are mutated (resulting in the mutated regions highlighted in the enzyme active site illustration above), phenylketonuria arises.<ref name="blau"> Blau, Nenad, Francjan Van Spronsen, and Harvey Levy. "Phenylkentonuria." The Lancet 376.9750 (2010): 1417-1427. Web. </ref>. The two mutations may occur in any of the exons, intervening introns, or perhaps in other regions such as the promoter.

Loss of PAH activity results in increased concentrations of phenylalanine in the blood and toxics in the brain. In addition, dysfunctional PAH leads to the appearance, in urine, of metabolites that arise from the transamination of L-Phe to phenylpyruvate. <ref name= "flydal"/>. Phenylketonuria is classified by the severity of hyperphenylalaninaemia.<ref name= "blau"/>. The normal range of blood phenylalanine concentrations is 50–110 μmol/L. Individuals with blood phenylalanine concentrations of 120–600 μmol/L are classified as having mild hyperphenylalaninaemia; those with concentrations of 600–1200 μmol/L are classified as mild phenylketonuria; and concentrations above 1200 μmol/L denote classic phenylketonuria. <ref name= "blau"/>.

== References ==

'''Symptoms'''

The common signs and symptoms associated with phenylketonuria include: progressive intellectual impairment, depression, and purposeless movement. <ref name= "flydal"/>. Other symptoms that have been noted encompass eczematous rash, autism, seizures, and motor deficits. <ref name= "blau"/>. However, the classic symptoms are those of neurophysiological and psychiatric impairments.

'''Molecular Explanation'''

The correlation between PAH malfunction and neurological deterioration can be explained as follows. The accumulation of phenylalanine inhibits the function of the aminoacid transporter 1 (LAT 1) at the brain's entry. <ref name= "blau"/>. This is detrimental because such transporter mediates the entry of other amino acids such as tyrosine and tryptophan into the brain. <ref name= "blau"/>. Once this transporter carrier is impaired, such amino acids are unable to cross into the brain. These aromatic amino acids serve as precursors to the synthesis of important neurotransmittors- tyrosine is a precursor for dopamine and norephinephrine, and tryptophan is a precursor for serotonin. Their absence then immensely disrupts the production of important neurotransmitters, hence resulting in the neurological impairment seen with phenylketonuria.

'''Treatment'''

There does not seem to be any medicinal treatment available to alleviate the symptoms of phenylketonuria. The most important step in managing this condition is dietary phenylalanine monitoring and restriction and this usually begins immediately after confirmation of hyperphenylalaninaemia in a neonate. <ref name= "blau"/>. Patients with phenylketonuria have to accept the phenylalanine-free formula and avoid foods rich in protein as well as foods and drinks containing aspartame, flour, and soya. Low-protein natural foods such as potatoes, some vegetables, and most cereals can be eaten but only in severely restricted amounts. Luckily, low-protein variants of some foods exist, such as low-protein bread and low-protein pasta. <ref name= "blau"/>. Diet monitoring and management has been shown to very successful in controlling phenylketonuria and halting its progression.

= References ==

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@@ Line 71: / Line 71: @@
 == Phenylketonuria ==
-Dysfunctional PAH consequently prevents the conversion of L-phenylalanine into L-tyrosin. This leads to the accumulation of phenylalanine in the blood. This subsequent increase in the concentration
+'''Overview'''
+Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. <ref name="lendly"> Lendley, Fred, Anthony DeLilla, and Savio Woo. "Molecular Biology of Phenylalanine Hydroxylase and Phenylketonuria." Trends in Genetics 1(1985): 309-313. Web.</ref>. It is genetic autosomal recessive disorder and a relatively common condition affecting approximately 1 in 10,000 newborn infants in the USA and Europe. <ref name="lendly"/>. The Phenylhydroxylase enzyme gene consists of 13 exons and introns and when both alleles are mutated (resulting in the mutated regions highlighted in the enzyme active site illustration above), phenylketonuria arises.<ref name="blau"> Blau, Nenad, Francjan Van Spronsen, and Harvey Levy. "Phenylkentonuria." The Lancet 376.9750 (2010): 1417-1427. Web. </ref>. The two mutations may occur in any of the exons, intervening introns, or perhaps in other regions such as the promoter.
+Loss of PAH activity results in increased concentrations of phenylalanine in the blood and toxics in the brain. In addition, dysfunctional PAH leads to the appearance, in urine, of metabolites that arise from the transamination of L-Phe to phenylpyruvate. <ref name= "flydal"/>.  Phenylketonuria is classified by the severity of hyperphenylalaninaemia.<ref name= "blau"/>. The normal range of blood phenylalanine concentrations is 50–110 μmol/L. Individuals with blood phenylalanine concentrations of 120–600 μmol/L are classified as having mild hyperphenylalaninaemia; those with concentrations of 600–1200 μmol/L are classified as mild phenylketonuria; and concentrations above 1200 μmol/L denote classic phenylketonuria. <ref name= "blau"/>.
-== References ==
+'''Symptoms'''
+The common signs and symptoms associated with phenylketonuria include: progressive intellectual impairment, depression, and purposeless movement. <ref name= "flydal"/>. Other symptoms that have been noted encompass eczematous rash, autism, seizures, and motor deficits. <ref name= "blau"/>. However, the classic symptoms are those of neurophysiological and psychiatric impairments.
+'''Molecular Explanation'''
+The correlation between PAH malfunction and neurological deterioration can be explained as follows. The accumulation of phenylalanine  inhibits the function of the aminoacid transporter 1 (LAT 1) at the brain's entry. <ref name= "blau"/>. This is detrimental because such transporter mediates the entry of other amino acids such as tyrosine and tryptophan into the brain. <ref name= "blau"/>. Once this transporter carrier is impaired, such amino acids are unable to cross into the brain. These aromatic amino acids serve as precursors to the synthesis of important neurotransmittors- tyrosine is a precursor for dopamine and norephinephrine, and tryptophan is a precursor for serotonin. Their absence then immensely disrupts the production of important neurotransmitters, hence resulting in the neurological impairment seen with phenylketonuria.
+'''Treatment'''
+There does not seem to be any medicinal treatment available to alleviate the symptoms of phenylketonuria. The most important step in managing this condition is dietary phenylalanine monitoring and restriction and this usually begins immediately after confirmation of hyperphenylalaninaemia in a neonate. <ref name= "blau"/>. Patients with phenylketonuria have to accept the phenylalanine-free formula and avoid foods rich in protein as well as foods and drinks containing aspartame, flour, and soya. Low-protein natural foods such as potatoes, some vegetables, and most cereals can be eaten but only in severely restricted amounts. Luckily, low-protein variants of some foods exist, such as low-protein bread and low-protein pasta. <ref name= "blau"/>. Diet monitoring and management has been shown to very successful in controlling phenylketonuria and halting its progression.
+= References ==
 <references />