iap-ahmedabad-inborn error of metabolism

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 > = 16--- excess acid production

Metabolic acidosis

• Approach is to give Na HCO3

• If unresponsive to HCO3-- IEM

Hyperammonemia

• Normal ammonia level- < 50 umol/l

• > 200 -- 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

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 !