PKU Phenylketonuria

What is PKU? PKU (phenylketonuria), is a rare, inherited metabolic disease that affects the way the body processes protein. People with PKU cannot process a part of the protein called phenylalanine. Thus, when untreated, phenylalanine builds up in the blood stream and causes brain damage. When a very strict diet is begun early and well- maintained, effected children can expect normal development and a normal life span.PKU (phenylketonuria), is a rare, inherited metabolic disease that affects the way the body processes protein. People with PKU cannot process a part of the protein called phenylalanine. Thus, when untreated, phenylalanine builds up in the blood stream and causes brain damage. When a very strict diet is begun early and well- maintained, effected children can expect normal development and a normal life span.

PKU Biomechanics The disease arises from the absence of a single enzyme (phenylalanine hydroxylase). This enzyme normally converts the essential amino acid, phenylalanine, to another amino acid, tyrosine. Failure of the conversion to take place results in a buildup of phenylalanine. Through a mechanism that is not well understood, the excess phenylalanine is toxic to the central nervous system and causes the severe problems normally associated with PKU. Not every child has the same degree of enzyme deficiency, however; some have enough enzyme activity that the diet can be quite liberal, while others must have the very strict diet. The nature of the diet for an individual child must be determined by an experienced PKU treatment program.The disease arises from the absence of a single enzyme (phenylalanine hydroxylase). This enzyme normally converts the essential amino acid, phenylalanine, to another amino acid, tyrosine. Failure of the conversion to take place results in a buildup of phenylalanine. Through a mechanism that is not well understood, the excess phenylalanine is toxic to the central nervous system and causes the severe problems normally associated with PKU. Not every child has the same degree of enzyme deficiency, however; some have enough enzyme activity that the diet can be quite liberal, while others must have the very strict diet. The nature of the diet for an individual child must be determined by an experienced PKU treatment program.

PKU Inheritance 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. When two carriers conceive a child, there is a one in four (or 25%) chance for each pregnancy that the baby will have PKU. The incidence of carriers in the general population is approximately one in fifty people, but the chance that two carriers will mate is only one in Carrier tests are available only through PKU treatment programsPKU 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. When two carriers conceive a child, there is a one in four (or 25%) chance for each pregnancy that the baby will have PKU. The incidence of carriers in the general population is approximately one in fifty people, but the chance that two carriers will mate is only one in Carrier tests are available only through PKU treatment programs

PKU Location The gene is located on the p arm of chromosome 12.

PKU & the Guthrie Test Newborns are pricked in the heel to analyze a drop of bloodNewborns are pricked in the heel to analyze a drop of blood The blood is added to a nutrient plate containing a auxotrophThe blood is added to a nutrient plate containing a auxotroph The auxotroph will grow with the addition of phenylalanineThe auxotroph will grow with the addition of phenylalanine The higher level of phenylalanine in the blood of a PKU babyThe higher level of phenylalanine in the blood of a PKU baby will allow the auxtroph to grow indicating an affected babywill allow the auxtroph to grow indicating an affected baby The Guthrie Test is a Mandatory Newborn Screening TestThe Guthrie Test is a Mandatory Newborn Screening Test Applied to babies after birth in all 50 states and most countriesApplied to babies after birth in all 50 states and most countries

PKU Effects NeurologicalNeurological Mental retardation Mental retardation Infantile irritability Infantile irritability Peculiar gait Peculiar gait Peculiar stance and sitting posture Peculiar stance and sitting posture Limb posturing Limb posturing Purposeless movements Purposeless movements Increased deep tendon reflexes Increased deep tendon reflexes Seizures Seizures Defective myelin formation Defective myelin formation DermalDermal Pale pigmentation Pale pigmentation Dry skin Dry skin Eczema Eczema Scleroderma Scleroderma Affected children usually have blond hair and blue eyes with cataracts Affected children usually have blond hair and blue eyes with cataracts

PKU Diet Individuals with PKU receive a diet containing limited phenylalanine. Foods such as meat, fish, eggs, cheese, milk products, legumes, and bread, which are high in PHE are eliminated or greatly reduced. Artificial protein substitutes are given which contain amino acids without phenylalanine. These formulas, such as Phenex-1 and Phenylfree, are designed to meet the specific needs of children with PKU.Individuals with PKU receive a diet containing limited phenylalanine. Foods such as meat, fish, eggs, cheese, milk products, legumes, and bread, which are high in PHE are eliminated or greatly reduced. Artificial protein substitutes are given which contain amino acids without phenylalanine. These formulas, such as Phenex-1 and Phenylfree, are designed to meet the specific needs of children with PKU. Your child cannot survive on formula alone. Some phenylalanine is necessary in his or her diet. This is essential for growth and is taken as a specific amount of breast milk or regular infant formula for babies, or food exchanges in older children.Your child cannot survive on formula alone. Some phenylalanine is necessary in his or her diet. This is essential for growth and is taken as a specific amount of breast milk or regular infant formula for babies, or food exchanges in older children.

Monitoring PKU This graph represents the average monthly PHE levels monitored monthly after birth in January, and over 2 weeks after 6 months of age. The baby was born with an extremely high level of PHE, which was controlled by diet. It can be seen that after June, the PHE levels remain, more or less, within the upper and lower limits. With this type of continual control, the parents and child can most likely expect normal physical and mental development.

Genetic Advice - - There is hope, if treatment begins at infancy. - - Maintain a diet that is low in Phenylalanine. - - Contact the NSPKU for help. - Numerous other support groups. - Numerous other support groups.

The National Society for Phenylketonuria (NSPKU) The National Society for Phenylketonuria (NSPKU) - Exists to help and support people with PKU, their families, and careers. - Exists to help and support people with PKU, their families, and careers. - Promotes the care and treatment of PKUs and works closely with medical professionals.- Promotes the care and treatment of PKUs and works closely with medical professionals. - O rganizes conferences and publishes a wide range of publications (including food lists)- O rganizes conferences and publishes a wide range of publications (including food lists) - Share experiences in managing PKU, specifically sharing cooking tips, low protein recipes, issues related to diet management, low protein food sources, and information about other support groups. - Share experiences in managing PKU, specifically sharing cooking tips, low protein recipes, issues related to diet management, low protein food sources, and information about other support groups.