Phenylketonuria (PKU) is a hereditary condition that is connected with the mutation of a gene known as phenylalanine hydroxylase (PAH). PAH works in conjuction with a cofactor referred to as tetrahydrobiopterin (BH 4 ) in the conversion of Phenylalanine (Phe) to tyrosine (Tyr). Phenylketonuria emerges when there is inadequate PAH or BH 4 in the blood. This inadequacy leads to the accumulation of Phenylalanine in the blood to toxic levels which may permanently impair the victim’s intellectual capability if not treated on time (Hafid & Christodoulou, 2015). The condition is mostly passed by untreated mother to a newborn. The prevalence of PKU varies widely across the globe and cannot be categorized as an ethnic phenomenon. It has been evidenced in one out of every 10,000 newborns among the Caucasians with Northern Europe reporting most of the incidences. Finland has the least number of incidences, reporting one in every 100,000 infants born alive. Turkey has the highest prevalence worldwide with one in every 4000 newborns. Australia reports roughly 25 cases annually (Hafid & Christodoulou, 2015). The implication is that PKU is a real phenomenon though not frequently reported in some countries.
Background
PKU was discovered by Asbjorn Folling in 1934 and aligned with exhibition of abnormally high levels of phenylpyruvic acid, a factor referred to as consanguinity and highly associated with the parents (Macdante & Kliegman, 2014). It is an autosomal recessive condition as it requires the two PAH genes in a human’s liver to be mutated. Individuals with a single gene mutation do not depict any PKU signs. In most cases, the parents of the victim are carriers of PKU, meaning that each one of them has a single, mutated PAH gene. Each parent gives a gene to ensure the development of the embryo in the mother’s womb. Babies who are born with the PKU condition inherited one gene from the mother and the other from the father, both of which had mutations. In cases where the baby inherits one gene that is mutated, he or she becomes a PKU carrier like the parents (BioMarin Pharmaceutical Inc., 2014).
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In the process of exchanging genes for the development of a baby, there is a 25% chance that each parent passes the mutated gene, thus giving rise to a baby with the PKU condition. The probability of each parent passing on the normal gene to the baby is also 25%, meaning that parents who are PKU carriers can give rise to a normal, PKU-free baby. The probability of one parent passing a normal gene and the other passing a mutated gene is 50%. The implication is that parents who are carriers of the PKU condition have a higher chance of bringing forth a carrier than a normal or PKU-infected baby. The chances of bringing forth a normal or an infected baby are equal. PKU can also arise as an environmental condition that aligns with excessive consumption of phenylalanine in one’s diet (Hafid & Christodoulou, 2015).
PKU is classified into four types, including classic, variant, mild, and hyperphenylalaninemia, which are dependent on the severity of Phenylalanine concentrations in the blood. The classic type depicts the highest severity with concentrations of 20mg/dL. Variant PKU is defined by moderate concentrations of between 15mg/dL and 20mg/dL. Mild PKU depicts the lowest levels of Phe concentration in the blood, approximated at 10mg/dL to 15mg/dL. Hyperphenylalaninemia entails a depiction of Phe levels that go slightly above the normal. Currently, health guidelines recommend the maintenance of Phe levels between 2mg/dL and 6mg/dL. As such, individuals whose levels range from 6mg/dL to 10mg/dL are categorized under the hyperphenylalaninemia type (Biomarin Pharmaceutical Inc., 2014). This reinforces the need for frequent check-ups so that one gets appropriate intervention before the deterioration of Phe levels to the classic type.
Major Symptoms of PKU
In most cases, a baby who is born with the PKU condition will depict no symptoms during the first two months after birth. In the third month, however, such children start depicting a disinterest with their surroundings. By the time they are one-year-old, signs of delayed development are evident. The skin of such children is also pale with rashes and this is accompanied by blue eyes that result from the body’s inability to change phenylalanine into melanin, the element responsible for the specific humans’ coloration (Genetics Home Reference, 2017). Where early treatment is not pursued early in life, the child may develop irreparable brain damage leading to permanent intellect problems. The condition may also culminate into social and behavioral problems. PKU may further result in shaky or jerking movements of arms and legs as well as mildew odor in breath, urine, or skin due to the surplus phenylalanine in the blood (Genetics Home Reference, 2017). The implication is that PKU is a condition that requires parental seriousness from the time of conception through birth to the various child developmental phases. Women with PKU are advised to adopt a diet that has low levels of phenylalanine if they have plans of becoming pregnant. PKU’s adverse effects can be mitigated if such a diet is followed before conception and in the entire pregnancy period (Scriver and Kaufman, 2001). It is, therefore, imperative that parents with the PKU condition be advised regularly to ensure that they adhere to the dietary prerequisites which will save them the agony of catering to the needs of a child with irreparable brain damage, which happens to be one of the signs of persistent negligence.
Diagnosis and Treatment
Screening is the first stage in the PKU diagnosis. Some states have screening programs that stipulate testing of the baby’s blood soon after birth for signs of PKU so that medical intervention can be actualized early enough to address any adverse effects in alignment with this condition (Hafid & Christodoulou, 2015). PKU is one of the rare medical conditions that are not readily curable. It is also a condition that demands close attention throughout one’s life for those who readily exhibit its signs. Where PKU is detected early enough, management and control of phenylalanine through an appropriate diet or dietary and medical intervention can enable the affected offspring to develop normally and also eliminate chances of brain damage. The latter is the worst situation that can occur to an individual who is born with this condition and occurs when appropriate interventions are not actualized early enough to manage the levels of Phe in the blood. It is the surplus Phe that amasses in the blood to toxic level leading to the deterioration of brain tissues and eventual damage that cannot be remedied (Hafid & Christodoulou, 2015). It is for this reason that PKU is considered a serious condition that requires keenness from the time it is detected, particularly with a parent who has intentions of bringing forth children and seeing them develop in a normal and appropriate manner.
Dietary Intervention
People who strictly adhere to the dietary specifications that enable the management and control of Phe in the blood depict no symptoms of PKU and the condition is only detectible in the test of their blood samples. Dietary therapy is the main treatment option that seems to work for PKU. Women have are PKU-positive have the big burden of ensuring adherence to the dietary prerequisites throughout pregnancy and after the birth of the child. Those who follow this recommendation have managed to offer a normal life to their children, where they develop like any other normal child though some of them depict a lower IQ (Hafid & Christodoulou, 2015).
Dietary intervention requires a reduction in the consumption of Phe-rich food, particularly proteins, such as egg whites, chicken breast, soybeans, turkey, fish, nuts, spirulina, lobsters, and legumes, among others. Foods sourced from grains and cereals, such as bread and pasta, also have significant amounts of Phe and should be consumed moderately (Marcdante & Kliegman, 2014). Dairy products also fall in the category of foods that are rich in proteins and also exhibit high levels of Phe and, therefore, require restrictive consumption (Hafid& Christodoulou, 2015). Consumption of natural foods containing high levels of starch and low protein levels, such as potatoes and peas, is allowed but also in moderation.
Supplementation is also an appropriate therapy for PKU-persons. This is necessitated by the body requirement for minerals, essential amino acids, vitamins, and some other nutrients that may be missed in the course of moderating Phe levels. Tyrosine supplements are particularly crucial in enabling brain development and must, therefore, be supplemented since Tyrosine is derived from Phe under normal circumstances yet Phe consumption is restricted in the dietary therapy as a remedial tactic for PKU. Protein substitutes are also good in controlling Phe levels as they help in halting the protein catabolism process which is the stimulant for the release of Phe from the muscles into the blood (Grȕnert, et. al, 2013). Fasting is also not allowed for PKU patients as it facilitates catabolism. A diet that is low in Phe but excludes protein substitutes may also not be effective in moderating Phe since nutritional insufficiency also hastens catabolism. The implication is that a PKU patient should be cautious in following prescription formula given by his or her medical care practitioner.
Limitations of the Dietary Intervention
Dietary intervention has been effective in eradicating the intellectual impairment that align with the PKU condition and restoring the IQ of such patients to considerable levels of normalcy. However, this intervention comes with some challenges in the course of its implementation as a therapy for PKU persons. First, the unpalatability of the recommended diet may hinder a patient’s compliance with the prescribed formula. Secondly, there are no guarantees of eradicating the persistence of neurological issues and, therefore, the patient’s quality of life still has loopholes. Third, the restrictive diet has potential for boosting nutritional insufficiency which may lead to other deficiencies. Finally, the patient’s family experiences monetary burden due to the huge cost of adhering to the food specifications and supplements (Hafid & Christodoulou, 2015).
Conclusion
PKU is a hereditary condition that arises from the mutation of the PAH gene. For it to occur in a child, both the mother and the father must offer the mutated gene to make a mutated pair since the condition is autosomal recessive. PKU is prevalent in Northern Europe with Turkey reporting the highest rates in the world. No cure has readily been found for this condition and the patients rely on their capacity to manage and control Phe levels in the blood with the assistance of a medical practitioner who offers a prescription formula. The dietary intervention is mostly the element of consideration in determining the prescription formula with the patient striving to consume small amounts of foods rich in proteins, which are also the Phe-rich elements. Of great concern is the probability of a permanent brain damage that culminates into intellectual incapacity where PKU is not diagnosed early enough. Mothers are particularly overburdened with the role of managing the Phe levels in their diet and that of the fetus before conception, during pregnancy, and after birth. Other symptoms of PKU, as may be evidenced in a baby after two months from birth, include a disinterest in the surroundings, delays in development, pale skin and blue eyes, and shaky arms and legs during movement. The dietary treatment, though effective in addressing intellectual incapacity, is limited by the unpalatability of the prescribed formula and the probability of boosting other nutritional deficiencies, among others. As such, PKU emerges as one of the serious rare conditions that demand the keenness of parents before and after conception, as a way of ensuring normal development of the baby.
References
Biomarin Pharmaceutical Inc. (2014). Causes and types of PKU. Retrieved from http://www.pku.com/understanding-pku/causes-and-types-of-pku/#sthash.GPMrjI8c.dpbs
Genetics Home Reference (2017). Phenylketonuria. Retrieved from https://ghr.nlm.nih.gov/condition/phenylketonuria.pdf
Grȕnert, S. C., Brichta, C. M., Krebs, A., Clement, H., Rauh, R., Freischhaker, C., … Schwab, K. O. (2013). Diurnal variation of phenylalanine and tyrosine concentrations in adult patients with Phenylketonuria: Subcutaneous microdialysis is no adequate tool for the determination of amino acids concentrations. Nutrition Journal, 12 (60), 1-12. Doi: http://www.nutritionj.com/content/12/1/60.
Hafid, N. A. & Christodoulou, J. (2015). Phenylketonuria: A review of current and future treatments. Translational Pediatrics,4 (4), 304-317. Doi: 10.3978/j.issn.2224-4336.2015.10.07.
Marcdante, K. & Kliegman, R. M. (2014). Nelson essentials of pediatrics e-Book (7 th ed.) . Elsevier Health Sciences.
Scriver, C. R. & Kaufman, S. (2001). The Hyperphenylalaninemias. In Scriver, C.R., Kaufman, S., Eisensmith, E., Woo, S. L. C., Vogelstein, B. & Childs, B. (eds.) The metabolic and molecular bases of inherited disease, 8 th ed. New York, NY: McGraw Hill.
