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

Individually rare, collectively a significant health problem

Approx 1:5,000 live births.

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

May be gradual May be sudden May be catastrophic

Infectious disease

Respiratory Cardiac GI Neurological

Metabolic acidosis

Hyperammonemia

Hypoglycemia

Aminoacidopathies or Galactosemia

Infection

Obtain plasma ammonia

Normal High anion Gap Normal anion gap

Acidosis

Urea Cycle defects Organic acidemias

Metabolic Disorder

High

Obtain blood pH and CO2 Obtain blood pH and CO2

Normal

Poor feeding Vomiting, dehydration, Tachypnea, seizures, Coma

Transient hyperammonemia

of the newborn

No acidosis

Obtain plasma amino acids

Normal or low

Acidosis

CPS deficiency or NAG synthetase

deficiency

Specific amino acid elevation

Obtain urine orotic acid

No specific amino acid elevation

Obtain blood pH and CO2

Obtain plasma citrulline

Normal or elevated

Low

OTC deficiency

HHH syndrome

Argininosuccinic acidemia

ArgininemiaCitrullinemiaOrganic acidemias

Obtain organic acids

High

Copyright ©1998 American Academy of Pediatrics

Can be life threatening event requiring rapid assessment and management.

ABC’s

CBC BloodCx if uncertain

Coags- PT/PTT BSR,RFTs, Ca and LFTs LP- r/o Meningitis, ABG-acidosis NH4 Lactate, Pyruvate , UA-ketones, urine

reducing substances, lactate

Correct hypotension.

NPO, reverse catabolism with D5-D10 1-1.5 x maint.

Correct hypoglycemia.

Correct metabolic acidosis.

Lactulose; Dialysis, if High/toxic NH4 › (nl is <35µmol/L)

Search for and treat precipitants; ie: Infection, dehydration.

Sepsis + ABx if uncertain.

Pyridoxine for neonatal sz. if AED no-response

.

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?

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

Treatment: Hydration with D10 + electrolytes D/C all protein x 24 hours—calories from

CHO and fat Remove ammonia Na phenylacetate/Na benzoate Give arginine Peritoneal dialysis if above measure fail Protein restriction for life

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

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- dialysis Carnitine After stabilization, may resume oral

feeds Consult dietitian, and metabolic

specialist

**Autosomal recessive inheritance** Examples are MCAD, LCAD, VLCAD Defect in acyl-CoA Dehydrogenase important in

fasting state. KEY features: Acute attack of life-threatening coma with

Hypoglycemia Absence of urine ketones, and reducing substances, +/- mild acidosis, or hyperammonemia, elevated

LFTs, abnl coags. +/-Hepatomegaly-/+ Dx with serum Acylcarnitine Profile or fibroblast

enzyme assay Treat ment: correct hypoglycemia with 10%D/W

and avoid fasting

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

specific IEM