PKU - BIO 162

Slide 1:PHENYLKETONURIA Phe, PAH, PKU and YOU It�s been a long time that I actually had to stop for a second and try real hard to read a word correctly� This one had me for more than a few minutes� I could hear my 1st grade teacher saying.. �you just have to take your time and sound it out.� Fennel- Ket- ten- or- ia � Not so bad� But not so fast -we�re not done yet�CLICK

Slide 2:Phe needs PAH or you get PKU Phenylalanine (Phe) Phenylalanine hydroxylase (PAH). Amino acid found in high protein foods Enzyme produced by the liver needed to process Phe There�s a few more like it� Lets look at the easy way first� Phe needs PAH or YOU get PKU � Got it? CLICK (Phe), phenylalanine (Fennel- Al- ah-neen) is�found in foods containing protein. (Protein is made up of around 20 separate building blocks called amino acids). Foods such as dairy products, red meat, chicken, fish, eggs, nuts, beans and lentils are high in protein.

Slide 3:What happens without PAH? Levels of Phe build up in the body Undersized neurons develop in cerebral cortex Damage to the brain results Without the enzyme, levels of phenylalanine - PAH, Phe, build up in the body to toxic levels. CLICK Because nerve cells are especially sensitive to phenylanine These substances are harmful to the central nervous system and cause brain damage by essentially poisoning the neurons of the brain. CLICK If phenylaline levels are not reduced it will result in undersized neurons that fail to make enough connections with other neurons CLICK Damage to the brain is irreversible CLICK

Slide 4:Symptoms of PKU Delayed mental and social skills Head size significantly below normal Hyperactivity Jerking movements of the arms or legs Mental retardation Seizures Skin rashes Tremors Unusual positioning of hands If untreated a child will develop symptoms � The most significant, here in RED- CLICK Delayed mental and social skills Head size significantly below normal Hyperactivity Mental retardation Jerking movements of the arms or legs Seizures Skin rashes Tremors Unusual positioning of hands Head size significantly below normal, Hyperactivity Mental retardation Are the most widespread and noticeable symptoms CLICK

Slide 5:Microcephaly Markedly smaller head Here is an example of Microcephaly- Noticed how the head is much smaller than average. This has been referred to as Pinhead in the past. CLICK

Slide 6:His sister, also diagnosed with PKU, has been treated successfully This 11 yr old child was untreated for PKU at birth Treatment at an early age is crucial and can stop the permanent damage to the brain. Here is a stunning example of the difference simple treatment can make in a child�s life. This child on the left was untreated early in life. Shortly after he was born, major advances were quickly made in the way PKU works and treatment for the condition. Within a few years his sister was born with the same condition, but was treated successfully since birth. The difference in startling. CLICK --- CLICK

Slide 7:What causes PKU to happen? Caused by a faulty gene on Chromosome 12 What causes PKU to occur? CLICK PKU is an inherited disorder, caused by a faulty gene on Chromosome 12. It is on Chromosome 12 where the PAH gene produces the instruction to create the PAH enzyme. CLICK

Slide 8:What causes PKU to happen? Caused by a faulty gene on Chromosome 12 In people with PKU a mutation changes the shape of the PAH enzyme which prevents the gene from functioning. In PKU the gene is defective causing a complete or near complete deficiency of the enzyme. CLICK

Slide 9:Etymology and History 1934 Asbjorn Folling Observed a �musty� odor to several retarded patients Discovered it was a result of excessive phenylacetic acid in the urine. Name is a description of that condition Phenyl keton uria (PKU) The etymology of the Disease- CLICK Asjborn Folling � Doctor in Norway, (where PKU is often called Folling�s Disease). �Folling was unique character. In medical history he marks a watershed because he was the first to Clarify and document that psychiatric diseases can have an entirely chemical cause.� He was first trained as a chemist and later studied medicine. Which was unusual at that time. He was also professorship of nutrient research. The perfect combination of skills to discover this disease. CLICK In 1934 a persistent mother of two mentally retarded children insisted Dr. Folling study them. He didn�t think he could offer much help to her but he accepted. As part of a routine examination he tested their urine for ketones, as in diabetics. The test indicated the first clue to the problem. CLICK Through his knowledge of organic chemistry, he eventually concluded they had Phenylpyruvic acid in the urine. Normal people did not. The children were unable to metabolize phenylalanine normally. The name of this condition derives from this mechanism

Slide 10:Genetic Characteristics Father is a �silent carrier� Mother is a �silent carrier� PKU develops when each parent who has two PAH genes on chromosome 12 � One is normal, but one is mutated. Shown here in red PKU is carried through an "autosomal recessive" gene. This means that two people who conceive a child must both be "silent carriers" of the gene in order for there to be a chance that the baby will have PKU..� CLICK � CLICK

Slide 11:Genetic Characteristics Father is a �silent carrier� Mother is a silent carrier When two carriers conceive a child, there is a one in four (or 25%) chance for each pregnancy that the baby will have PKU. CLICK

Slide 12:Genetic Characteristics Father is a �silent carrier� Mother is a silent carrier The incidence of carriers in the general population is approximately one in fifty people, CLICK But the chance that two carriers will mate is only one in 2500. Carrier tests are available only through PKU treatment programs.�

Slide 13:Prevalence of PKU around the world CLICK PKU affect approximately 50,000 people worldwide The �incidence�of PKU varies widely in different human populations around the world. CLICK in�Norway, it is the most rare. Fewer than one in 100,000 people are diagnosed with PKU� CLICK In contrast, Turkey the highest rate in the world, 1 in 2600 births show PKU CLICK Ireland, is not far behind Turkey with approximately 1 in 4,500 births resulting in PKU, CLICK Ireland has many more cases than Finland which has approximately �1 in 13,000. � CLICK In the United States, about 1 in 15,000 births show classical PKU with a higher incidence among those whose ancestors are Native American or from Northern Europe. CLICK

Slide 14:Screening Since the mid 1960�s Infants are routinely screened at birth Because of the very positive outcome when children are treated early and well, newborn screening for PKU is carried out in every state in the US and in many other countries. Such screening started in the mid-1960's. Although PKU affects only one out of every approximately 15,000 babies born in the US, there are several hundred babies diagnosed and put on the diet each year. PKU can be easily detected with a simple blood test. All states in the US require a PKU screening test for all newborns as part of the newborn screening panel. The test is generally done by taking a few drops of blood from the baby before the baby leaves the hospital CLICK

Slide 15:Primary Treatment Careful, strict attention to a special diet �Diet For Life� PKU is a treatable disease. Treatment involves a diet that is extremely low in phenylalanine, particularly when the child is growing. The diet must be strictly followed. This requires close supervision by a registered dietitian or doctor, and cooperation of the parent and child. Those who continue the diet into adulthood have better physical and mental health. �Diet for life� has become the standard recommended by most experts. This is especially important before conception and throughout pregnancy. CLICK

Slide 16:�Diet For Life� Meat Chicken Fish Nuts Cheese Legumes Milk The diet requires severely restricting or eliminating foods high in Phe, such as�meat,�chicken,�fish,�eggs,�nuts,�cheese,�legumes,�milk�and other dairy products. Starchy foods, such as�potatoes,�bread,�pasta, and�corn, must be monitored. Infants may still be breastfed to provide all of the benefits of breast milk, but the quantity must also be monitored and supplementation for missing nutrients will be required. CLICK

Slide 17:�Diet For Life� Ever notice that weird warning on the side of diet soda and NutraSweet? Ever notice that weird warning on the side of diet soda and NutraSweet? CLICK The sweetener�aspartame also known as Equal and NutraSweet are present in many diet foods and soft drinks. CLICK These must also be avoided, as aspartame consists of two amino acids: phenylalanine and aspartic acid which would exacerbate the problem. CLICK

Slide 18:New Treatments Kuvan was introduced in 2007 Pharmaceutical version of BH4 which is found naturally in the body BH4 assists in the breaking down of Amino Acids Until 2007, the strict Diet For Life was the only treatment for PKU CLICK Only recently has the FDA approved a drug that has shown to significantly lower the Phe levels in PKU patients- Kuvan is a pill that is taken once a day in effort to counteract dangerous Phe levels in the blood by providing a synthetic version of BH4. CLICK In the body, the enzyme (PAH) converts (Phe) into tyrosine in the presence of (BH4). BH4 is a natural substance found in the body that helps reduce Phe to safe levels in the blood. In PKU, the PAH enzyme doesn't work well and too much Phe builds up in the blood. High levels of Phe affect the brain if left untreated. CLICK The active ingredient in KUVAN is a pharmaceutical version of BH4. It works in the same way as the body's BH4. KUVAN adds more BH4 and stimulates the PAH enzyme to �wake up� and process Phe in PKU patients. The PAH enzyme begins to convert Phe to tyrosine, and helps to keep your blood Phe levels low. Early results have shown this drug to be very effective and widely used among PKU patients. CLICK

Slide 19:Support Organizations While PKU is relatively rare when compared to many other diseases, because it is so critical and high maintenance condition, a strong national and international network of Support organziations exist to help parents carefully guide their children into their new lifestyle. CLICK The national PKU Alliance acts as a flagship to the dozens of other support sites and message forums for patients and families of those affected by PKU, as well as important legislative issues and medical research about PKU. CLICK Another very helpful source of information to PKU patients is PKU News. PKU News does an especially good job of showing other PKU patients inspiring stories of other PKU patients who are succesfully making it through the challenges of living with this difficult diease. CLICK

Slide 20:References "Phenylketonuria: What Is It?"�Your Genes, Your Health. Dolan DNA Learning Center. Web. 12 Dec. 2011. <http://www.ygyh.org/pku/whatisit.htm>. "Recently Diagnosed?"�National PKU Alliance. Web. 12 Dec. 2011. <http://www.npkua.org/index.php/recently-diagnosed-2>. Food and Drug Administration (FDA). FDA Approves Kuvan for Treatment of Phenylketonuria (PKU), December 13, 2007. "What Is PKU."�Children's PKU Network. Web. 12 Dec. 2011