IndexPhenylalanine MetabolismWhat is PhenylalaninePhenylalanine MetabolismFurther Tyrosine MetabolismPathophysiology of PhenylketonuriaWhat is PhenylketonuriaPathophysiology of PKUGenetics and Inheritance of PKUS Symptoms, Diagnosis and Treatment of PKU Symptoms PKUSDia gnosisTreatmentExplaining blood test resultsPregnancy and PKUBreastfeedingNeonatal testing for metabolic disordersConclusionREFERENCESThe scenario presents a 4-month pregnant woman with phenylketonuria (PKU). Due to the teratogenic effects that phenylalanine has on the fetus, her family doctor advised her to follow a low-protein diet. The discomfort this caused Nuria pushed her to drastically change her eating habits to the point that, after her monthly blood test, her family doctor became concerned. The family doctor then decided to refer Nuria to a PKU treatment center for a nutritional assessment and genetic counseling. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an Original EssayIn the following paragraphs I will explain the following learning objectives.Unknown TermsPhenylalanine MetabolismPathophysiology of PKUGenetics and Inheritance of PKUDiagnosis, Symptoms and Treatment of PKUExplanation of Nuria's Blood Test ResultsPKU and PregnancyNeonatal Test for Metabolic DiseasesUnknown TermsTeratogenic= a term that describes a substance that can cause disruption or abnormal development of a fetus resulting in birth defects. The word comes from the Greek word for monster "τέρας". [Chanapa, T. (2014).]Microcephaly= a condition in which the fetal head is smaller than normal caused by substances that can cause brain damage in vivo including alcohol, cigarette smoking and in this case phenylalanine. [MedicineNet. (2019).]Mental retardation= when an individual has intellectual abilities at or below IQ 70 along with an impaired ability to perform independent daily functions. [Webster, M. (2019) ]Phenylalanine MetabolismWhat is PhenylalaninePhenylalanine is an essential aromatic amino acid and is a precursor of tyrosine which in turn is a precursor of catecholamines such as tyramine, dopamine, epinephrine and norepinephrine. Phenylalanine can be found in high concentrations in the brain and plasma. An average adult should digest 5-8 g of phenylalanine per day. [National Center for Biotechnology Information] Phenylalanine Metabolism Phenylalanine can be metabolized to tyrosine by phenylalanine hydroxylase in the presence of molecular oxygen and the coenzyme tetrahydrobiopterin (BH4) with one molecular oxygen becoming the hydroxyl group on the tyrosine and the other being reduced to water. While BH4 is oxidized to dihydrobiopterin (BH2), which is regenerated via dihydropteridine reductase which requires NAHD. [A. Harvey, R. and Ferrier, D. (2019).]Further Metabolism of TyrosineSince tyrosine is made up of an essential amino acid, it constitutes a nonessential amino acid in the body. Tyrosine is the precursor of catecholamines; dopamine, norepinephrine and epinephrine. First, tyrosine is hydroxylated by tyrosine hydroxylase to form 3,4-dihydroxyulphenylalalnine (DOPA). Then DOPA is further decarboxylated to form dopamine via pyridoxal phosphate which is then hydroxylated by dopamine beta-hydroxylase to produce norepinephrine. Norepinephrine is then n-methylated via S-adenosylmethionine to produce epinephrine. DOPA could be converted by tyrosinase into dopaquinone and then form melanin in the skin epidermis, particularly in melanocytes. Another important metabolite ofTyrosine are thyroid hormones. The final metabolites of phenylalanine metabolism are fumarate and acetoacetate which are used to produce energy. In the case of PKU, side reactions to phenylalanine producing phenylpyruvate and phenylethylamine may occur. These byproducts cause aminoaciduria, which is an excess of amino acids in the urine. [A. Harvey, R. and Ferrier, D. (2019).]Figure 1:A diagram showing the different metabolites resulting from phenylalanine and the catalyst and byproducts of each reaction. [Fernanda Schuck, et al. (2015).]Pathophysiology of phenylketonuriaWhat is phenylketonuriaPhenylketonuria is an inherited protein metabolic disorder associated with the inability of an individual to metabolize phenylalanine resulting in accumulation of the substance in the body due to the lack of the enzyme phenylalanine hydroxylase or dihydrobiopterin reductase. [Al Hadif, N. and Christodoulou, J. (2015).], [Pietz, J., et al. (1999).]Pathophysiology of PKUSince phenylalanine cannot be metabolised in the body, this suggests that on a normal diet an affected individual would have an increased concentration of phenylalanine in the blood plasma, which in turn is toxic to the brain. The pathophysiology of PKU is not completely understood, however there are 2 hypothesized models [A. Dyer, C. (1999).]. The first is that increased concentrations of phenylalanine in the brain cause neurotoxicity. Furthermore, the lack of neurotransmitters produced by the metabolism of phenylalanine to tyrosine, such as dopamine, could cause the adverse effects of PKU. [Schuck et al. (2015).]Genetics and inheritance of PKUA briefly explained before PKU is an autosomal recessive disease caused by mutation of phenylalanine hydroxylase (PAH) located on chromosome 12q23.2 or by many aminoactive mutations in the PAH locus affecting the coenzyme tetrahydrobiopterin (BH4) which gives rise to non-PKU HPA [Robin A Williams, J., et al. (2008).]. Inactive or less effective PAHs would discourage the metabolism of phenylalanine to tyrosine and its constituents. [Reference, G. (2019).]Autosomal would suggest that it only affects the 22 non-sex chromosomes and recessive would mean that for an individual to have the phenotype of this disease they must inherit one allele from each parent [Reference, G. (2019).] . In this case, the mother is affected since the father is not affected and is not a carrier, so the probability of the child having the disease is 0%, however 50% of him is a carrier. If the father were a carrier then the probability of the child having the disease would be 50% and of being a carrier would also be 50%. Figure 2: An illustration showing the inheritance pattern of an autosomal recessive disease when both parents are carriers. carriers of the defective gene. [Plus, M. (2019).]SYMPTOMS, DIAGNOSIS AND TREATMENT OF PKUSI symptoms symptoms occur when the condition is not treated early in life. The effects of phenylalanine can include damage to the brain and nervous system resulting in learning difficulties. Other symptoms may include: [NHS (2019).], [NIH. (2019).]Behavioral difficultiesLighter skin, hair and eyes due to reduced melanin productionEczemaRecurrent vomitingJerky movements of arms and legsTremorsEpilepsyMusky odor of breath, skin and urineGrowth delayMicrocephaly or small head sizeDiagnosisBlood spot screening on newborns would be conducted to show increased levels of phenylalanine in the blood using tandem mass spectroscopy. Genetic screening to show the presence of a PAH gene mutation. This could also be used to explain the genetic inheritance of your disease and the likelihood of your child having the disease. [Cindie, S.(2017).]TreatmentThere is no cure for PKU, however symptoms can be controlled with a strict diet. This includes eating a low-protein diet while avoiding high-protein foods. This would include: [NIH. (2019).]MeatEggsNutsSoya beansDairy productsControlling intake of other foods such as potatoes and grainsSpecial avoidance of aspartame as it can be metabolised in the body to phenylalanine.Protein should not be completely excluded from the diet as phenylalanine is an essential amino acid therefore it cannot be metabolised by the body. Since tyrosine cannot be produced in the body, supplementation would be necessary. You may also be prescribed medications such as sapropterin dihydrochloride, brand name Kuvan, which is an approved treatment for PKU. Kuvan is a form of BH4 that helps the body break down phenylalanine. However, one reason a person cannot break down phenylalanine is having too little BH4. Therefore, the use of Kuvan only helps some people reduce the amount of phenylalanine in the blood. Kuvan alone will not reduce the amount of phenylalanine to the required level and therefore should be used in conjunction with the PKU diet. [Rohr, F., et al (2004).] Genetic counseling should be conducted in cases of genetic disorders, such as Nuria's. This usually involves: [NHS. (2016).]How parents should approach if their child is affectedProvides information on the possibility of other family members being carriersBuild a support group around parents and those affectedThe family doctor has recommended this action due to the Nuria's fear that her son might also be affected by PKU. This way she will be able to learn how genetic traits are transmitted and the probability that her child will have the disease will also depend on her husband's genotype. Blood test results explained Low levels of hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV) and ferritin could be linked to the drastic dietary changes Nuria implemented on herself to ensure her son was not exposed to high levels of phenylalanine. From the test results it can be deduced that she has an iron deficiency which could cause microcytic anemia. Due to his further low protein diet, he may not be able to get enough iron from food as iron is a high protein food such as meat, fish and nuts. [Eatright.org. (2019).]However, as folate is replaced for pregnant women, there is no decrease in folate in the blood sample. Pregnancy and PKU Before and during conception, women with PKU must follow a strict diet to protect the fetus from the teratogenic effects of high levels of phenylalanine in the maternal blood which can be transferred to the fetus through the placenta. Dietary management together with newborn screening have significantly reduced the morbidity of untreated PKU in childhood. Therefore phenylalanine levels should be measured 2 to 3 times per week along with amino acids, vitamins, minerals and trace elements. Tyrosine should also be supplemented with various vitamins and minerals. Ultrasound scans could be used to check for microcephaly, however the definition of microcephaly is controversial as there is no clear definition of the term. [R. Carol, M., et al. (2018)].BreastfeedingPhenylalanine levels in the breast milk of affected women are higher than normal. However, breastfed babies should have a normal level of phenylalanine so that breastfeeding cannot cause adverse effects if the baby does not have the disease. [Acog.org. (2015).]Neonatal testing for disordersmetabolicA complete examination must be carried out within 72 hours of birth. This would include checking the child's eyes with a flashlight to assess movement, the heart for any abnormal heart sounds such as a murmur, and the hips to check the joints, which if left untreated could cause permanent joint problems in the future. A hearing test would also be helpful. conducted by a healthcare professional before the baby is discharged or 4-5 weeks after birth. Hearing defects can affect a child's development, so early diagnosis is necessary to increase the likelihood of developing speech, language and communication skills. As mentioned above, testing for PKU would require a blood sample. This involves a healthcare worker bricking the baby's heel to get 4 drops of blood onto a special paper. Then your blood can be tested for 9 rare and serious conditions, including: Keep in mind: This is just a sample. Get a custom paper from our expert writers now. Get a Custom Essay Sickle Cell Anemia Cystic Fibrosis Congenital Hypothyroidism Phenylketonuria (PKU) Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) Maple Syrup Urine Disease (MSUD) Isovaleric Acidemia (IVA) Glutaric Acidity Type 1 (GA1) Homocystinuria ( HCU) [NHS. (2018).]ConclusionIn conclusion, this scenario highlights the need for people with PKU to seriously monitor their diet to combat the adverse effects that increased phenylalanine would have in their body. Especially for pregnant women, like Nuria, since out of fear that her condition could affect the baby, she exposed herself to anemia. In cases like these, special treatment centers would be needed for nutritional assessment and guidance. Genetic counseling helps families to understand the measures to take if their child is affected, or even to explain to them the probability of having an affected child. REFERENCESISA. Dyer, C. (1999). PATHOPHYSIOLOGY OF PHENYLKETONURIA. [online] Wiley Online Library. Available at: https://onlinelibrary.wiley.com/doi/epdf/10.1002/%28SICI%291098-2779%281999%295%3A2%3C104%3A%3AAID-MRDD2%3E3.0.CO%3B2-7 [ Accessed February 18, 2019].A. Harvey, R., & Ferrier, D. (2019). Biochemistry. 5th ed. Lippincott, Williams & Wilkins, pp.278-282.Acog.org. (2015). Management of women with phenylketonuria - ACOG. [online] Available at: https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Genetics/Management-of-Women-With-Phenylketonuria?IsMobileSet=false [ Accessed 18 February 2019]. Al Hadif, n. and Christodoulou, J. (2015). Phenylketonuria: a review of current and future treatments. [online] PubMed Central (PMC). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728993/ [Accessed 18 February 2019].Chanapa, T. (2014). Teratogenic | The Encyclopedia of the Embryo Project. [online] Embryo.asu.edu. Available at: https://embryo.asu.edu/pages/teratogens [Accessed 18 February 2019].Cindie, S. (2017). Phenylketonuria: causes, symptoms and diagnosis. [online] Health line. Available at: https://www.healthline.com/health/phenylketonuria#treatments [accessed February 18, 2019].Eatright.org. (2019). Foods to combat iron deficiency. [online] Available at: https://www.eatright.org/health/wellness/preventing-illness/iron-deficiency [Accessed February 18, 2019]. Fernanda Schuck, et al. (2015). Pathophysiology of phenylketonuria: on the role of metabolic alterations. Aging and Illness, 6(5), p.390.MedicineNet. (2019). Prognosis, causes, symptoms and diagnosis of microcephaly. [online] Available at: https://www.medicinenet.com/microcephaly/article.htm#microcephaly_facts [accessed 18. 2019].