1. Supplements and Co-factors in the Treatment of Metabolic Disorders Lynne A. Wolfe, MS, CRNP, BC Metabolic Nurse Practitioner Children’s Hospital of Pittsburgh

2. UREA CYCLE SUGAR FAT PROTEIN Mitochondria TCA ETC ATP C C Food Groups of Metabolic Disease

3. Current Therapy for Metabolic Disease Avoid Catabolism Newborn Weight Loss Febrile Illnesses, trauma, surgery Provide Calories from “non-offending” foods groups

4. Current Therapy of Metabolic Disease Replace “created” deficiencies Calcium and other macro/micronutrients Carnitine Essential Fatty acids

5. Current Therapy of Metabolic Disease Provide elements not released or able to be used from apoenzyme Biotin - Biotinidase def Cobalamin

6. Current Therapy of Metabolic Disease Remove Toxic build up Carnitine in OA’s & FOD’s Glycine - Isovaleric acidemia Sodium Benzoate and Dextromethorphan - Nonketotic Hyperglycinemia Sodium Phenylbutyrate - Urea Cycle disorders

7. Current Therapy of Metabolic Disease Go around metabolic block or create a block we can manage MCT Oil - Long chain FOD’s Orfadine (NTBC) - Tyrosinemia

8. Current Therapy of Metabolic Disease Augment Enzyme function Riboflavin - FOD’s, GAII Biotin - Propionic acidemia

9. UREA CYCLE SUGAR FAT PROTEIN Mitochondria TCA ETC ATP C C Food Groups of Metabolic Disease Serum Amino acids Ammonia Abnormal Urine Organic acids Low Carnitine Alanine Lactate / Pyruvate BCAA

10. Current Treatment Restrict Offending Amino acids Supplement single Amino acids as needed Carnitine supplementation Add calories with carbohydrates and fats Biotin, Glycine in specific disorders +/- Antibiotics (Flagyl)

11. ? Potential New Treatments BH4 supplementation - PKU Enzyme Replacement - PKU CoQ Antioxidant Vitamins LNAA supplementation More aggressive Organ Transplantation

12. UREA CYCLE SUGAR FAT PROTEIN Mitochondria TCA ETC ATP C C Food Groups of Metabolic Disease Serum Amino acids Ammonia Abnormal Urine Organic acids Nl/Low Carnitine Alanine Lactate / Pyruvate

13. Current Treatment Strict, very low protein diet Single Amino acid supplements Sodium Phenylbutyrate/Acetate/Benzoate +/- B Vitamins +/- Carnitine

14. ? Potential New Treatments IV Phenylbutyrate/acetate Gene therapy

15. UREA CYCLE SUGAR FAT PROTEIN Mitochondria TCA ETC ATP C C Food Groups of Metabolic Disease Abnormal Urine Organic acids Nl/Low Carnitine Alanine Lactate/ Pyruvate Abnormal Acylcarnitines

16. Current Treatment Avoid Fasting Low Fat diet, provide extra calories with Protein and Carbohydrates MCT Oil in long chain defects +/-Essential Fatty acid supplements +/- DHA +/- Riboflavin +/- Carnitine Avoid Toxins (Depakote etc…)

17. ? Potential New Treatments Creatine CoQ Antioxidant Vitamins

18. Other supplements ? Cornstarch Glutamine Inulin (FOS fiber) Antibiotics Senna Periactin (Cyproheptadine) Zofran (Ondansetron)

19. QUESTIONS ????? THANK YOU