Phenylketonuria (PKU) Disease: Inborn Error

PhenylketonuriaNameInstitutional AffiliationDate Phenylketonuria Phenylketonuria (PKU) is an inborn error on the metabolism of amino acids that can be detected during the first days of birth if appropriate blood testing is carried out on the child CITATION Mar14 \l 1033 (Mark, Elaine, Jill, Paul, & Mary, 2014). There are also different terms that are used to refer to phenylketonuria condition. Such include Classical Phenylketonuria, Hyperphernylalanemia, Phenylalaninemia, Folling Disease, and Phenylalanine Hydroxylase DeficiencyCITATION Bla101 \t \l 1033 (Blau, Spronsen, & Levy, 2010). PKU is characterized by the absence of Phenylalanine Hydroxylase enzyme that is involved in the processing of one of the essential amino acids in the body called phenylalanine. Phenylalanine amino acids are present in most of the protein foods that we take. Amino acids are the building blocks of proteins that are involved in the growth and development of different cells in the body. Under ordinary circumstances, phenylalanine is supposed to be converted to a different form of amino acid that is called tyrosine that is used by the body in growth and development. However, if it occurs that the enzyme (phenylalanine hydroxylase) is not in the body, then phenylalanine will not be converted into its appropriate form and it will instead accumulate in the blood which will later affect the brain tissues CITATION Jah14 \l 1033 (Jahja, Huijbregts, & Sonneville, 2014). After birth, the symptoms that are associated with PKU cannot be observed at first. As mentioned earlier, the condition can be detected if one carries out a blood test of the newborn. Given that the disease cannot be easily detected, the National Human Genome Research Institute reports that most of the hospitals located in the US carry out a blood test on the newborns to ensure that there is an early diagnosis which will lead to early treatment CITATION Nat101 \l 1033 (National Human Genome Research Institute, 2010). In most of the instances, infants suffering from PKU appear to be abnormally drowsy and they experience difficulties when they are feeding CITATION Bil16 \l 1033 (Bilder, Noel, Baker, & Irish, 2016). The untreated infants also appear to be lightly pigmented with light eyes, hair and even the skin. This is due to the high levels of phenylalanine in the body, they will interfere with the chemical that is responsible for maintaining melanin CITATION Bil16 \l 1033 (Bilder, Noel, Baker, & Irish, 2016). Rashes can also be observed on the skin of the infants and it is accompanied by blistering, itching and redness on the areas that have been affected. In addition, developmental retardation is observed in children with PKU who have not gone through treatment. The average IQ of the children who are untreated in most cases is less than 50 CITATION Bil16 \l 1033 (Bilder, Noel, Baker, & Irish, 2016). The main organ affected by the disease is the brain and therefore infants with PKU can suffer from mental retardation that progressively becomes severe. There are also additional neurologic symptoms that can accompany the infants such as the occurrence of seizures due to uncontrolled electrical activities that take in the brain, hyperactivity due to abnormally increased activities, difficulties in coordination which causes a strange style of walking also called gait CITATION Bil16 \l 1033 (Bilder, Noel, Baker, & Irish, 2016). Due to the presence of the by-products of phenylalanine in the urine and sweat of the infant, one can smell a strange odor. There are also cases of PKU that are less severe referred to non-PKU hyperphenylalaninemia or variant PKU. Patients who experience symptoms that are less severe have a lower risk of brain damage. Women who suffer from PKU can have uncontrolled phenylalanine levels and they give birth to babies who are at a high risk of intellectual disability due to lower IQ, a low birth weight, heart-related problems and in some cases slow growth CITATION Bil16 \l 1033 (Bilder, Noel, Baker, & Irish, 2016). The untreated females also show spontaneous abortions or delays in the fetal growth, a condition that is referred to as intrauterine growth retardation. The National Human Genome Research Institute reports that PKU condition occurs in 1/10,000-15,000 newborns CITATION Nat10 \l 1033 (National Human Genome Research Institute, 2010). It can also be inherited from the parents. In cases of inheritance, PKU is inherited in the form of a recessive pattern. The pattern works by copying both genes in the cell that have mutations. The autosomal condition will be carried in the mutated genes of the parents and the parents will not be showing the symptoms. Instead, the symptoms will develop on the newborn when the parents will donate the above-mentioned condition to their newbornCITATION Bla16 \t \l 1033 (Blau, 2016). Children born to women who are suffering from PKU have an abnormally small head and other facial abnormalities. There is also a relationship that exists between the severe symptoms that are observed with the high levels of phenylalanine in the blood of the mother. Due to this, the women with PKU who have stopped their treatment procedure need to be taken through diet before the conception and they should be on the diet through their pregnancy period CITATION Els06 \l 1033 (Elson & Buck, 2006). Neurological symptoms are observed in some of the patients with phenylketonuria and they vary widely. For instance, the seizures are observed approximately in 25% of the older children CITATION Nat10 \l 1033 (National Human Genome Research Institute, 2010). The abnormalities are observed through the brain wave tests (EEG) in 80% of the PKU patientsCITATION Adl \l 1033 (Adler-Abramovich, Vaks, Carny, & Trudler, 2012). There are also other common neurological symptoms such as spasticity (difficulties in the movement of muscles), muscles that are tighter (hypertonicity) and even an increase in the tendon reflexes. Approximately 5% of the infants who show signs of PKU become challenged physically CITATION Amb \l 1033 (Amber, Sonneville, & Francois, 2011). When a child with PKU is conceived, different processes take place in the body of the mother and child. The mother is the one who metabolizes the compounds in the body of the child before delivery. The mother can do it correctly despite the fact that she is the carrier of the gene that causes PKU. If the newborn begins feeding, then the milk proteins will be broken down and they will release the amino acids that are metabolized. However, as the amino acids are broken down, the conversion of phenylalanine into tyrosine is interfered with since PAH has not correctly been formed and hence there will be an accumulation of phenylalanine in the blood of the newborn. As such tyrosine that is used in the synthesis of proteins used by the baby to grow will be synthesized in insufficient quantities that will make the child have a metabolic defectCITATION Amb \l 1033 (Amber, Sonneville, & Francois, 2011). The balance that is needed for metabolism to work correctly will be lost and there would be negative consequences for the baby such as delayed development. Delayed development takes more time to be noticed and it is noticed after some months have passed. PKU as a disease does not shorten the life expectancy of a person regardless of whether they go for treatment procedures or they do not go for appropriate treatment procedures. In some cases where both the parents are genetic of the condition then the probability of them giving birth to a PKU infant is 1 out of 4. In the US, the rate of occurrence of the condition is 0.01%CITATION Bla11 \t \l 1033 (Blau, Hennermann, & Langenbeck, 2011). Patients who are suffering from PKU are treated in a metabolic clinic that has a wide range of restrictions on the foods that contain phenylalanine CITATION Phy10 \l 1033 (Phyllis, 2010). It makes it easier for them to monitor phenylalanine levels of the patient as they undergo treatment. Significant Causative Factors Phenylketonuria is a genetic disease. Like the other genetic diseases, phenylketonuria is determined by the two genes that are ; one that is inherited from the father and the other one from the mother. The recessive genetic disorders will occur when the individual will inherit the same abnormal gene that has the same trait from their parents. If it happens that the inborn receives one normal gene and another one that contains a gene for the disease, then the person will only be a carrier of the disease and under such circumstances, such people do not show any symptoms that are associated with the disease. As mentioned previously, the risk of passing the defective gene by two parents who are carriers of the gene to the affected child is usually 25% for each of the pregnanciesCITATION Bla16 \t \l 1033 (Blau, 2016). In addition, the risk of the parents with the above condition to have a newborn who is a carrier just like them is usually 50% CITATION Els06 \l 1033 (Elson & Buck, 2006). Consequently, the chance for the child to receive genes that are normal from the parents is 25%CITATION Bla16 \t \l 1033 (Blau, 2016). The gene that causes PKU is found on the long arm of chromosome 12CITATION Bla16 \t \l 1033 (Blau, 2016). However, it should be noted that the genetic mutations for the children with PKU may be different in some cases. There are more than 300 different mutations in the PKU gene that can be identified. Since the different mutations that are associated with PKU cause a variance on the levels of phenylalanine that are found in the blood, the diet of each of the child needs to be adjusted to create a tolerance of the amino acid. Various laboratory tests that have been carried out over a long period of time reveal that the levels of phenylalanine in blood plasma is 20-60 times more than that is found in blood plasma at the normal levelsCITATION Cam12 \t \l 1033 (Camp & Lloyd-Puryear, 2012). The symptoms mentioned in the previous part develop due to the existence of a defective liver enzyme called phenylalanine hydroxylase that plays a role in the metabolisms of phenylalanine to tyrosineCITATION Cam12 \t \l 1033 (Camp & Lloyd-Puryear, 2012). A retardation in the mental state of the child is due to the lower levels of phenylalanine in the brain that destroys myelin which is a fatty covering of the nerve fiber found in the brain CITATION Ant13 \l 1033 (Antenor-Dorsey & T Hershey, 2013). Depression also comes in and it reduces the levels of dopamine and serotonin found in the brain. Research on PKU has also revealed that the risk of infection among the African Americans is lower as compared to the other ethnic origins (US Department of Health and Human Services, 2018). Treatment In the treatment of PKU, it is important to note that its goal should be to ensure that the levels of phenylalanine in the blood plasma are kept within a range of 2-6mg % near to the normal range of 1mg% CITATION Els06 \l 1033 (Elson & Buck, 2006). The above can be achieved through a diet that is strictly planned and monitored at all times. Since phenylalanine is an essential amino acid, limiting its intake in the diet of the child should be done with utmost care. A diet that is well maintained in some cases can prevent mental retardation and other related problems in the life of the child. It is also important to begin the treatment procedure as early as possible when the child is below three months to avoid incidences of mental retardation. However, there are other studies that have shown that children who have gone through a late treatment procedure can also do well CITATION Bil16 \l 1033 (Bilder, Noel, Baker, & Irish, 2016). It applies to PKU children who are treated with a low phenylalanine diet before the age of three months and with an IQ range that is normal CITATION Els06 \l 1033 (Elson & Buck, 2006). Controlling the phenylalanine intake is significant for PKU patients. When they stop controlling their intake of phenylalanine, then there are neurological changes that can occur in their bodies such as a decline in the IQ CITATION Jah14 \l ...