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

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

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

Signs and Symptoms Respiratory Cardiac GI Neurological Infectious disease

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

Presentation Metabolic acidosis Hyperammonemia Hypoglycemia

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

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

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

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

Hypoglycemia Glucose level helps in the differential diagnosis

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?

Copyright ©1998 American Academy of Pediatrics

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

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

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

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

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

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

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

Thank you !