1. Approach to Inborn Error of Metabolism in a Neonate Filomena Hazel R. Villa, MD PL2

3. Objectives To recognize IEM in a neonate with non- specific signs and symptoms To make use of simple lab tests in the diagnosis of IEM To know the initial management of life threatening conditions associated with IEM

4. Signs and Symptoms May be gradual May be sudden May be catastrophic

5. Signs and Symptoms Respiratory Cardiac GI Neurological Infectious disease

6. Categories of IEM Disorders of: Amino acids Carbohydrates Fatty acid Lysosomal and peroxisomal function Mitochondrial Organic acids

7. Presentation Metabolic acidosis Hyperammonemia Hypoglycemia

8. Metabolic acidosis pH <7.35 Excess H+ HCO3 deficit Calculate anion gap –Na – (Cl + HCO3) –Normal is 8-16meq/l

9. Metabolic Acidosis If Chloride is increased- HCO3 wasting GI or renal disorders If Chloride is Normal and Anion gap is > = 16---  excess acid production

10. Metabolic acidosis Approach is to give Na HCO3 If unresponsive to HCO3--  IEM

11. Hyperammonemia Normal ammonia level- < 50 umol/l > 200 --  IEM If within 24 hours of life; preterm, RD  THAN After 24 hours-  IEM

12. Hypoglycemia Glucose level helps in the differential diagnosis

13. STEPS: 1. Determine if there is metabolic acidosis 2. Is anion gap >16? 3. Is there hypoglycemia? 4. Is there hyperammonemia? –Within 24 HOL? –After 24 HOL?

14. Copyright ©1998 American Academy of Pediatrics

16. Healthy NB  rapidly ill, –Ketoacidosis, poor feeding Vomiting, dehydration Hypotonia, lethargy Tachypnea, seizures Coma, unusual odors Organic acidemia

17. Labs: Urine organic acids Ketonuria (in the NB)- pathognomonic of IEM Neutropenia, thrombocytopenia +/- hyperammonemia Abnormal acylcarnitine

18. Treatment: Stabilize Get rid of organic acid intermediates, and ammonia-  hemodialysis Carnitine After stabilization, may resume oral feeds Consult dietitian, and metabolic specialist Organic acidemia

19. Urea cycle disorder No acidosis (respiratory alkalosis) No ketones (unlike organic acidemia) No hypoglycemia But with hyperammonemia

20. Treatment: Remove ammonia Hydration with D10 + electrolytes D/C all protein x 24 hours—calories from CHO and fat Na phenylacetate/Na benzoate Give arginine Protein restriction for life Urea cycle disorder

21. Prognosis: guarded Even with Treatment, many will die Definitive treatment: liver transplant Urea cycle disorder

22. Summary Metabolic acidosis + hyperammonemia Request for specific lab studies Consult metabolic specialist Initial therapy- stabilize patient! Long term treatment- based on specific IEM

23. Thank you !