Phenylketonuria Introductory information Written by: P. Burgard - PowerPoint PPT Presentation

Phenylketonuria Introductory information Written by: P. Burgard & U. Wendel Reviewed & revised for North America by: S. van Calcar

Phenylketonuria PKU Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 2 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Phenylketonuria Phenylketones in urine PKU Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 3 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Hyperphenylalaninemia Too much Phenylalanine in blood HPA Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 4 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Food – Components of a normal diet Protein Fat Carbohydrates Protein consists of chains of amino acids Phenylalanine Tyrosine Valine Leucine Threonine Natural Food Protein Protein Protein Fat Fat Fat Carbohydrates Carbohydrates Carbohydrates eg . eg . eg . eg . eg . milk, yogurt, nuts meat, poultry, fish, fruit, vegetables, sugar, lemonade oil, margarine cheese, egg potatoes, cereals, rice, pasta Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 5 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Enzymes Enzymes are proteins that facilitate various chemical reactions in the body. They are involved in the biosynthesis (anabolism) and the degradation (catabolism) of all the substances in the body. This is called metabolism. P henyl a lanine H ydroxylase (PAH) is the enzyme that converts the amino acid phenylalanine to the amino acid tyrosine. In HPA/PKU, the activity of the PAH enzyme is deficient. Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 6 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Enzymes In order to function correctly, some enzymes need the help of cofactors (= coenzymes). PAH is such an enzyme and BH 4 is the cofactor. PAH requires BH 4 to become an active enzyme and function properly. + = PAH PAH BH 4 -Cofactor BH 4 -Cofactor PAH inactive PAH active Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 7 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

In a person without PKU – PAH works PAH Phenylalanine Tyrosine BH 4 -Cofactor BH 2 PAH is functional BH 4 supply is sufficient Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 8 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

In a person with PKU or HPA – PAH is deficient  Metabolic Block PAH Phenylalanine Tyrosine  BH 4 -Cofactor BH 2 PAH is not functional BH 4 supply is sufficient Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 9 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Hyperphenylalaninemias due to BH 4 -deficiency  Metabolic Block PAH Phenylalanine Tyrosine  BH 4 -Cofactor BH 2 PAH is functional BH 4 supply is insufficient Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 10 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Diagnosis of PKU Phenylalanine in dried blood spots Increased Newborn screening Normal Dried blood spots Phenylalanine in plasma Confirmation Increased of diagnosis Normal Venous blood Conversion of phenylalanine: At confirmation of hyperphenylalaninaemia: plasma phenylalanine concentrations 1 mg/dl ≈ 60 µmol/L range from 2.0 mg/dl to > 20 mg/dl (120 µmol/L to > 1200 µmol/L) Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 11 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Diagnosis of PKU Disorders of phenylalanine metabolism Mild Hyperphenylalaninaemia Phenylketonuria BH 4 -Cofactor deficiency (very rare) Special treatment Dietary management is Dietary management is necessary not necessary 4 10 Normal Phenylalanine concentration in blood (mg/dl) range Normal range in plasma: Phenylalanine: ca. 60-120 µmol/L (1.0 - 2.0 mg/dl) Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 12 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Pathogenesis High concentrations of phenylalanine damage the brain Phenylalanine > Impairment of brain development and function > Behavioral and intellectual disabilities > Information processing impairment Written by P. Burgard & U. Wendel Supported by Supported by as a service to metabolic medicine as a service to metabolic medicine 13 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Food – Components of a normal diet Protein Fat Carbohydrates Protein consists of chains of amino acids Phenylalanine Tyrosine Valine Leucine Threonine Natural Food Protein Protein Protein Fat Fat Fat Carbohydrates Carbohydrates Carbohydrates eg . eg . eg . eg . eg . milk, yogurt, nuts meat, poultry, fish, fruit, vegetables, sugar, lemonade oil, margarine cheese, egg potatoes, cereal, rice, pasta Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 14 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Principles of management Diet is very low in natural protein + metabolic formula that does not contain phenylalanine Natural Protein Phenylalanine Tyrosine Valine Leucine Threonine + a PKU formula that contains all amino acids except phenylalanine Natural Food Protein Protein Protein Fat Fat Fat Carbohydrates Carbohydrates Carbohydrates eg . eg . eg . eg . eg . milk, yogurt, nuts meat, poultry, fish, fruit, vegetables, sugar, lemonade oil, margarine cheese, egg potatoes, cereal, pasta, rice Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 15 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Dietary management during the first 4 to 6 months of life Natural Protein Phenylalanine Tyrosine Valine Leucine Threonine Breast milk or infant formula Phe-free infant formula Natural protein = PKU formula = all amino acids all amino acids with except phenylalanine phenylalanine included + Fat Fat Carbohydrates Carbohydrates Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 16 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Foods + special low-protein products + PKU formula Nutritional components of the PKU diet once the baby is weaned and solids are introduced Natural Protein Phenylalanine Tyrosine Valine Leucine Threonine + a PKU formula containing all amino acids except phenylalanine Special low Natural PKU formula protein Fat low-protein products food Carbohydrates eg . eg . eg . eg . vegetables, fruits, special breads, sugar, lemonade oil, margarine potatoes, some pasta and ready- cereals made meals Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 17 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.

Goals for management of PKU PKU-diet Very low-protein natural foods + special low-protein products + PKU formula Management Goals for all ages Long-term phenylalanine concentrations in blood should be: 2 to 6 mg/dl (120 to 360 µmol/L) Blood phenylalanine levels need to be measured frequently! Conversion of phenylalanine: 1 mg/dl ≈ 60 µmol/L Written by P. Burgard & U. Wendel Supported by as a service to metabolic medicine 18 Reviewed & revised for North America by S. van Calcar Dietary management of the condition should only be done under medical supervision.