Inborn Errors of Metabolism

Question 1

Clinical clues of IEM on physical exam

Answer 1

• Lethargy
• Hepatomegaly, Splenomegaly
• Hypotonia
• Jaundice, signs of liver failure
• Occasionally Dysmorphic, Coarse • Skin and hair abnormalities
• Cataracts
• Non-immune hydrops
• Odour

Question 2

Clinical clues of IEM on physical exam

Answer 2

• Hypoglycemia
• Metabolic acidosis → elevated anion gap 
• Respiratory Alkalosis
• Urine Ketones
– High: in newborn → metabolic disease 
– Low: in the sick child → disorder of ß-
Oxidation (= fatty acid oxidation) 
• Electrolytes
• Elevated lactate 
• Pancytopenia
Lots of causes other than IEMs

Question 3

First line work-up for suspected inborn error of metabolism

Answer 3

– Urine: Organic acids, Amino Acids, U/A
• ? Reducing substances
• ? Oligosaccharide & MPS screens (chronic,
coarse facies, hydrops, regression)
– Blood: Glucose, lytes, Ammonia, lactate (not
pyruvate), urate
• Amino acids
• Acylcarnitine profile
• Homocysteine
• Carnitine (total/free)→ often not useful • Copper, ceroluplasmin
– MRI/MRS (creatine, lactate, NAA)

Question 4

Beckwith-Wiedemann syndrome

• Triad
• things to monitor

Answer 4

E – exomphalos
M - macroglossia
G – gigantism

Monitor:
AFP- hepatoblastoma
US – Wilms tumour