PhenylketonuriaDefinition: Phenylketonuria (commonly known as PKU) is an inherited disorder thatincreases the levels of a substance called phenylalanine in the blood.Phenylalanineisabuildingblockof proteins(anaminoacid)that isobtainedthrough the diet. It is found in allproteins and in some artificialsweeteners. IfPKUisnot treated, phenylalaninecanbuilduptoharmful levelsinthebody,causing intellectual disability and other serious health problems.he signs and symptoms of PKU vary from mild to severe. he most severe formof this disorder is known as classic PKU. Infants with classic PKU appear normaluntil theyareafewmonthsold. !ithout treatment, thesechildrendeveloppermanent intellectual disability. "ei#ures, delayed development, behavioralproblems, and psychiatric disorders are also common. Untreated individuals mayhave a musty or mouse$like odor as a side effect of e%cess phenylalanine in thebody. &hildren with classic PKU tend to have lighter skin and hair than unaffectedfamily members and are also likely to have skin disorders such as ec#ema.'ess severe forms of this condition, sometimes called variant PKU and non$PKUhyperphenylalaninemia, have a smaller risk of brain damage. People with verymild cases may not re(uire treatment with a low$phenylalanine diet.)abies born to mothers with PKU and uncontrolled phenylalanine levels (womenwho no longer followa low$phenylalanine diet) have a significant risk ofintellectual disability because they are e%posed to very high levels ofphenylalanine before birth. hese infants may also have a low birth weight andgrowmoreslowlythanother children. *ther characteristicmedical problemsincludeheart defectsorotherheart problems, anabnormallysmall headsi#e(microcephaly), andbehavioral problems. !omenwithPKUanduncontrolledphenylalanine levels also have an increased risk of pregnancy loss.Metabolic pathway: P+, is an integral en#yme used to convert the amino acid Phenylalanine to theaminoacidyrosine. yrosineisthensubse(uentlycataly#edusinganotheren#yme, yrosine hydro%ylase (,). , functions in con-unction withtetrahydrobiopterin (),.), the same cofactor used with P+,, to produce '$/,.$dihydro%yphenylalanine, more commonly referred to as '$0*P+.Pathophysiology:he en#yme phenylalanine hydro%ylase normally converts the amino acidphenylalanine into the amino acid tyrosine. If this reaction does not take place,phenylalanineaccumulatesandtyrosineisdeficient. 1%cessivephenylalaninecan be metaboli#ed into phenylketones through the minor route, a transaminasepathway with glutamate. 2etabolites include phenylacetate, phenylpyruvate andphenethylamine. 1levated levels of phenylalanine in the blood and detection ofphenylketones in the urine is diagnostic, however most patients are diagnosedvia newborn screening.Phenylalanine is a large, neutral amino acid ('3++). '3++s compete fortransport across the blood4brain barrier ()))) via the large neutral amino acidtransporter ('3++). If phenylalanine is in e%cess in the blood, it will saturate thetransporter. 1%cessivelevelsof phenylalaninetendtodecreasethelevelsofother '3++sinthebrain. ,owever, astheseaminoacidsarenecessaryforprotein and neurotransmitter synthesis, Phe buildup hinders the development ofthe brain, causing intellectual disability.Etiology/ Causes:Genetics:his condition is inherited in an autosomal recessive pattern, which means bothcopies of the gene in each cell have mutations. he parents of an individual withan autosomal recessive condition each carry one copy of the mutated gene, butthey typically do not show signs and symptoms of the condition.Manifestations:2ost individuals with phenylketonuria (PKU) appear normal at birth. If newbornscreening fails, progressive developmental delay is the most commonpresentation. *ther findings in untreated children in later infancy and childhoodmay include vomiting, mousy odor, ec#ema, sei#ures, self$mutilation, and severebehavioral disorders.*lder individuals who cease dietary treatment in childhood may have evidence ofdemyelinationon25I. *ccasionally, deteriorationof cognitiveperformanceormotorskillsalsomaybepresent.Intelligence (uotients(I6s)may dropby78points or more if the diet is stopped in midchildhood.Diagnostic Procedures:"creening and presentationPKU is commonly included in the newborn screening panelof most countries,with varied detection techni(ues. 2ost babies in developed countries arescreened for PKU soon after birth.978: "creening for PKU is done with bacterialinhibition assay (;uthrie test), immunoassays using fluorometric or photometricdetection, or amino acid measurement using tandemmass spectrometry(2"