PKUPKUPhenylketonuriaPhenylketonuria

What is PKU?What is PKU?

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

PKU BiomechanicsPKU Biomechanics• The disease arises from the absence of a The disease arises from the absence of a

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

PKU InheritancePKU Inheritance

• PKU is carried through an "autosomal PKU is carried through an "autosomal recessive" gene. This means that two people recessive" gene. This means that two people who conceive a child must both be "silent who conceive a child must both be "silent carriers" of the gene in order for there to be a carriers" of the gene in order for there to be a chance that the baby will have PKU. When two chance that the baby will have PKU. When two carriers conceive a child, there is a one in four carriers conceive a child, there is a one in four (or 25%) chance (or 25%) chance for each pregnancyfor each pregnancy that the that the baby will have PKU. The incidence of carriers in baby will have PKU. The incidence of carriers in the general population is approximately one in the general population is approximately one in fifty people, but the chance that two carriers fifty people, but the chance that two carriers will mate is only one in 2500. Carrier tests are will mate is only one in 2500. Carrier tests are available only through PKU treatment programsavailable only through PKU treatment programs

PKU LocationPKU Location

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

PKU & the Guthrie TestPKU & the Guthrie Test

• Newborns are pricked in the heel to analyze a Newborns are pricked in the heel to analyze a drop of blooddrop of blood

• The blood is added to a nutrient plate The blood is added to a nutrient plate containing a auxotrophcontaining a auxotroph

• The auxotroph will grow with the addition of The auxotroph will grow with the addition of phenylalaninephenylalanine

• The higher level of phenylalanine in the blood The higher level of phenylalanine in the blood of a PKU baby of a PKU baby

• will allow the auxtroph to grow indicating an will allow the auxtroph to grow indicating an affected babyaffected baby

• The Guthrie Test is a Mandatory Newborn The Guthrie Test is a Mandatory Newborn Screening TestScreening Test

• Applied to babies after birth in all 50 states Applied to babies after birth in all 50 states and most countriesand most countries

PKU EffectsPKU Effects

• NeurologicalNeurological

Mental retardation Mental retardation

Infantile irritability Infantile irritability

Peculiar gait Peculiar gait

Peculiar stance and sitting Peculiar stance and sitting posture posture

Limb posturing Limb posturing

Purposeless movements Purposeless movements

Increased deep tendon reflexes Increased deep tendon reflexes

Seizures Seizures

Defective myelin formationDefective myelin formation

• DermalDermal

Pale pigmentation Pale pigmentation

Dry skin Dry skin

Eczema Eczema

SclerodermaScleroderma

Affected children usually have Affected children usually have blond hair and blue eyes with blond hair and blue eyes with cataractscataracts

PKU DietPKU Diet

• Individuals with PKU receive a diet containing limited Individuals with PKU receive a diet containing limited phenylalanine. Foods such as meat, fish, eggs, cheese, phenylalanine. Foods such as meat, fish, eggs, cheese, milk products, legumes, and bread, which are high in milk products, legumes, and bread, which are high in PHE are eliminated or greatly reduced. Artificial protein PHE are eliminated or greatly reduced. Artificial protein substitutes are given which contain amino acids without substitutes are given which contain amino acids without phenylalanine. These formulas, such as Phenex-1 and phenylalanine. These formulas, such as Phenex-1 and Phenylfree, are designed to meet the specific needs of Phenylfree, are designed to meet the specific needs of children with PKU.children with PKU.

  • Your child cannot survive on formula alone. Some Your child cannot survive on formula alone. Some

phenylalanine is necessary in his or her diet. This is phenylalanine is necessary in his or her diet. This is essential for growth and is taken as a specific amount of essential for growth and is taken as a specific amount of breast milk or regular infant formula for babies, or food breast milk or regular infant formula for babies, or food

exchanges in older children.exchanges in older children.

Monitoring PKUMonitoring PKU

This graph represents the average monthly PHE levels monitored monthly after birth in January, and over 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 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 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 upper and lower limits. With this type of continual control, the parents and child can most likely expect normal physical and mental development.expect normal physical and mental development.

Genetic AdviceGenetic Advice

-         - -         - There is hope, if treatment begins There is hope, if treatment begins at at infancy. infancy.

-       -   -       -   Maintain a diet that is low in Maintain a diet that is low in Phenylalanine. Phenylalanine.

-       -  -       -  Contact the NSPKU for help.Contact the NSPKU for help.

- Numerous other support groups.- Numerous other support groups.

  The National Society for The National Society for Phenylketonuria (NSPKU) Phenylketonuria (NSPKU)

- Exists to help and support people with PKU, their - Exists to help and support people with PKU, their families, and careers. families, and careers.

• - - Promotes the care and treatment of PKUs and Promotes the care and treatment of PKUs and works closely with medical professionals. works closely with medical professionals.

• - O- Organizes conferences and publishes a wide rganizes conferences and publishes a wide range of publications (including food lists) range of publications (including food lists)

- Share experiences in managing PKU, - Share experiences in managing PKU, specifically sharing cooking tips, low protein specifically sharing cooking tips, low protein recipes, issues related to diet management, low recipes, issues related to diet management, low protein food sources, and information about other protein food sources, and information about other support groups.support groups.