Classic Phenylketonuria

Classic PKU is the leading cause of high levels of phenylalanine in the blood system and will be the feature of this research paper. PKU once had irreversible and harmful damage to the people it affected. Infants that were born with the genetic condition were prone to the suffer from ruthless mental retardation and behavioral disorders as a result of no one having knowledge of what was causing the symptoms. It was not until 1934 when a biochemist by the name A. Folling from Norway, the disease was found out through the urine examination. Folling found out that the generic disease, which causes the affected individual’s body to not be able to contain a substance referred to as phenylalanine (phe), a vital amino acid available in protein. After the unearthing of the disease by Folling, an American scientist by the name George Jervis finally, in 1947, concluded that the precise cause was an enzyme found in the liver referred to as Phenylalnine hydroxylase (PAH). PAH is accountable for making surplus phenylalanine into tyrosine and various essential amino acids. Tyrosine is a useful amino acid that produces proteins, hormones as well as neurotransmitters that manage brain functions. The discovery of the distorted PAH enzyme made it possible exploring for a remedy. Earlier researchers reasoned that by excluding foods that had phe from the affected individual’s diet and providing them with vitamin supplements would halt the toxic effect of surplus phe and its derivatives in the system. Doctors soon realized the profound effects in the diet therapy and consequently patients, if treated early enough after birth can grow normally by following a medical diet (Orphanet, 2011).

Introduction

Phenylketonuria (PKU) is a generic condition that is typified by incapacity of the body to efficiently use the vital amino acid, phenylalanine. Amino acids essential building blocks for the body proteins. Vital amino acids can only be available from the food the body consumes, as the body does not always produce them. In case of “classic PKU”, the enzyme  that digests down phenylalanine and its’ digestion components from other enzyme routes, build up in the blood and body organs. Even though the expression ‘hyperphenylalaninemia’ strictly refers to eminent blood phenylalanine, it is normally used to portray a group of conditions other than classic PKU. These other conditions maybe as a result of a partial lack of the phenylalanine digestion enzymes of the lack of another enzyme essential for the processing of this amino acid. A standard blood phenylalanine level is approximately 1 mg/dl. In case of  classic PKU, levels may vary from 6 to 80mg/dl, but are normally higher than 30mg/dl . Levels are typically less in the other cases of hyperphenylalaninemia. Persistently high levels of phenylalanine as well some of its digestion products can lead significant brains malfunctions (Orphanet, 2011).

PKU is an autosomal generic disorder with phenotypic  features that thwart people form normally digesting phenylalanine (phe). Unattended, this generic biochemical condition thwarts normal brain growth and normally leads to severe mental retardation. Other phenotypic characteristics are skin diseases, seizures, extreme restlessness, violent behavior, and occasionally a moldy or mousy body color. For most of the affected individuals, these symptoms normally occur about two to three months after birth. Cure that is commenced after developmental harm has already taken place will only halt further harm from occurring and will assist in taking care of the odor, skin reaction, as well as restlessness. Luckily, discovery of the disorder immediately after birth, using a custom blood examination procedure, which came in place of the “wet diaper” test in 1964, has been a typical practice in each state and Canadian Province since 1991. The blood screening tests for phe levels in the blood plasma. If a baby has an elevated level of phe, confirmatory examinations are carried out during a 3 week stage, diagnosis is recognized and diet treatment commences early enough. Prenatal testing is uncommon and expensive as a result of the fact that PAH enzyme is only present in the liver it is not found in amniotic fluid, but skin cells can be tested by checking for transformation in the DNA (Pey, Stricher, Serrano & Martinez, 2007).

Although placing the infant on a phenylalanine-restricted diet during the first few weeks after birth, and upholding good diet management thereafter during growth years is efficient avoiding symptoms, PKU can still be a root to problems in a case where diet is not maintained all through to adulthood. This is particularly true in case of women with PKU. It is crucial for women to follow the medical diet during the period of their childbearing because of the harmful nature of high levels of phe can expose to the unborn child of a PKU mother. Maternal PKU has an effect on offspring with conditions, for instance, mental disorder, undersized brain size, innate heart disorder, underweight birth and impulsive abortion (Gonzalez, Willis, Monte, 2010). Examinations are still open to doubt indentifying whether preconception cure of mothers with PKU have lead to offspring with normal physical and intellectual skills. This is due to the children in this expansive research study are not yet mature enough to be adequately examined (Sarkissian, Gámez, Wang, Charbonneau, Fitzpatrick, Lemontt, et al 2008).

There are 5 various types of PKU disorders that varies from a mild to extreme defect in the PAH enzyme. Traditional PKU, where there is near to total nonexistence in activity of the PAH enzyme leads to about 60 percent of all PKU cases and is the extreme type. The PAH site or locus is on the end of the extended arm of chromosome 12. Its map position is 12q22-24.1 and it is regarded as a large gene being 90 kb containing 13 exons and hardwiring a polypeptide of a massive 452 amino acids (Gonzalez, Willis, Monte, 2010). Genetically, PKU is not normally originated from  a single gene imperfection because there are two other enzymes created by various genes that influence the efficiency of PAH. Nevertheless,  mutation in PAH gene is the primary determinant of PKU (Lee, Ridout, Walker, & Cockburn, 2005). There are in excess of 365 recognized likely mutant alleles that take part in PKU and 105 of the mutation are available on the gene encoding for PAH. Luckily, two-thirds of the entire mutant alleles are holed-up in four haplotypes. Majority of the PAH variants are single-base substitutions for instance mmissense, nonsense and splicing mutations. Ordinary instances of these single base replacements would be cases of splicing alteration in intron 12, missense alterations in exons 7,9 as well as 12 or a removal   in the area of exons 1 and 2 (Burton, Grange, Milanowski, Vockley, Feillet, Crombez et al. 2007).   

Although huge progress has been established since PKU’s unearthing in 1934, there are still barriers to tackle and more information to be processed. Present treatment of the PKU is carried with serious diet therapy. Nevertheless, other approaches are being examined. Plant enzyme referred to as phenylalanine ammonia-lyase has been previously examined with mice and likely to be an ingredient addition to the diet therapy owing to its likelihood to minimize phe levels in mice by 50 percent during a seven day period (Burton, Grange, Milanowski, Vockley, Feillet, Crombez et al. 2007). Another possibility to cure PKU is the option of liver transplant. Although liver disorder is not a symptom of PKU and not a common treatment option, a ten year old child affected by PKU and unassociated liver disease undergone a liver transplant which in turn treated him of PKU. A study involving gene therapy is still in process.

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