A 17 month old child with periodic Vomiting F.Ahmadabadi MD Child Neurologist

Positive findings Episodic Vomiting Periodic Acidosis Developmental delay Hyper uricemia Hyper triglyceridemia Organomegaly (Splenomegaly) Pancytopenia (Cyclic)

Approach to Vomiting I Increased ICP V Vascular O Obstruction M Metabolic disorders I Infections T Trauma-Toxins

We have a high anion gap Acidosis Metabolic acidosis Metabolic acidosis AG=Na +K-(Cl+HCO3)=140+5-(109+4)=32 We have a high anion gap Acidosis M U D P I L E S Metformin Uremia DKA Phenformin Iron Toxicity Lactic acidosis Ethanol Salcylate Methanol Paraldehyde IEM Ethylen Glycol

Causes of Hyperuricemia Alcoholic Ketoacidosis Diabetic Ketoacidosis Glycogen Storage Disease, Type Ia-TypeVII Gout Hemolytic Anemia Hodgkin Disease Hyperparathyroidism Hypothyroidism Nephrolithiasis Nephropathy, Uric Acid MCAD Barth syndrome 3-methylglutaconic aciduria Fanconi –Bickel syndrome

Causes of Hypertriglyceridemia Type 2 diabetes mellitus Cholestatic liver diseases Nephrotic syndrome Chronic renal failure Hypothyroidism Cigarette smoking GSD1 Drugs LPL Deficiency Glycerol kinase deficiency Lecithin cholesterol acyltransferase deficiency(LCAT)

Differential Diagnosis GSD s Organic acidemia Fatty acid oxidation disorders Acute metabolic decomponsation Chronic involvement of tissues Recurrent episodes of hypoketotic hypoglycemia Alteration in total carnitine

Differentia diagnosis GSDs Organic acidemia Organomegaly Hypertriglyceridemia Hyperuricemia Acidosis NDD Neutropenia But abcense of Hypoglycemia and normal facies is against it Acidosis Pancytopenia MS/MS NDD Vomiting Hyper ammonemia But high TG & Uric acid don’t confirm it

G6P deficiency(GSD type I) Ia Enlargedf liver and Kidneys Hyperlipidemia Hypoglycemia Ketoacidosis Seizure FTT TG and Uric acid High Renal involvement Ib Neutropenia Epinephrin Test

Debrancher deficiency(GSD III ) Hepatomegaly Hypoglycemia Short stature Myopathy Cardiomyopath Splenomegaly No kidney enlargement Normal uric acid PCO IIIa:Liver & Muscle III b:liver

GSD VI (Phosphorylase deficiency) Lactic and Uric acid normal No cardiac or Muscular involvement FTT Hypertriglyceridemia Hypoglycemia Benign

Organic acidemias (3.7 per 100,000) Propionic acidemia Methyl malonicacidemia Isovaleric acidemia Glutaric aciduria

Management Liver Biopsy Urine Organic acids EMG-NCV

Control of Hypoglycemia Control of Hyper ammonemia Correct the acidosis Correct the Liver function

Remarks :MS/MS The most important part is Carnitine profile. It is performed on Plasma or serum. Urine has not diagnostic value. Preferred specimen Collected after 6 h fasting or in acute illness In marked carnitine deficiencyLoad patient with carnitine

Cont, Antibiotics containing the Pivaloyl group(Pivoxilsulbactam)  False elevation of C5 MCT oil  Elevation of C8-C10 Carnitine  C2(Acethyl) ,C3 (Propionyl) Prolonged fasting  Increased C2 ,OH-C4 Lactic acidosis  Elevates C3

Cont, Higher than normal level of Free carnitine has not diagnostic value except CPT1 Def and severe cardiomyopathy. Carnitine level is high at birth then fall to half the adult value and normalized after a few months. Minor elevation(<1.5xUNL) of a single metabolite is not diagnostic. MCAD & VLCAD  Carnitine deficiency