JC 131 – Paediatric Chemical Pathology (*)

Question 1

Causes of Neonatal Jaundice

Answer 1

Question 2

First line investigations for NNJ

Answer 2

Bilirubin total and unconjugated

Blood:
 Blood count
 Prothrombin time

Renal:
 Plasma urea, electrolytes, glucose, acid-base, lactate
 Urinalysis for reducing substances
 Urinary pH and ketones

Mibi:
 Blood and urine culture, workup neonatal hepatitis

Question 3

2 types of hyperlactatemia

Answer 3

 Type A lactic acidosis = with hypoxia

 Type B lactic acidosis = without hypoxia

Question 4

Acquired causes of hyperlactatemia

Answer 4

 Hypoxia
 Exercise
 Seizure
 Severe dehydration
 Infections
 Severe catabolic state
 Poisoning

Question 5

Inherited causes of hyperlactatemia

Answer 5

 Disorders of lactate-pyruvate oxidation
 TCA cycle deficiencies
 Respiratory chain defects/ mitochondrial disease
 Disorders of gluconeogenesis
 Disorders of glycogen metabolism

Question 6

First line investigation for hyperlactatemia

Answer 6

– pyruvate

 To calculate lactate-to-pyruvate ratio
 To differentiate the genetic causes
 Note: for accurate measurement, add accurate volume of blood into the special bottle with perchloric acid immediately after blood taking

Question 7

First line investigations for hypoglycemia

Answer 7

Confirm hypoglycemia (obtain critical blood sample, urine)

Ketone:
- test acetoacetate and beta-hydroxybutyrate in urine by dipstix or quantitative measurement

• Ketone positive in urine =normal ketosis, use GC-MS to check urine organic acid
• Ketone negative in urine = Hypoketosis, measure serum insulin

Question 8

Ddx hypoglycemia with high urine ketones

Answer 8

High urine ketone = normal ketosis

Use GC-MS to check urine organic acid

Question 9

Ddx hypoglycaemia with low urine ketones

Answer 9

Measure serum insulin:

Question 10

Hyperammonemia

Ddx increase of orotic aciduria

Answer 10

Question 11

o Plasma urea: low
o Ammonia: high
o Plasma amino acids (diagnostic pattern): low arginine, elevated glutamine

What is this pattern

Answer 11

UCD (urea cycle defect)

UCD rarely presents with elevated urine orotic acid without elevation of ammonia; but a normal ammonia result (in fact high normal) cannot rule out UCD

Question 12

Further investigations of Hyperammonemia

Answer 12

Liver biopsy for testing

Peripheral whole blood genetic analysis: PCR and sequencing of OTC gene (mitochondrial enzyme ornithine transcarbamylase; X-linked)

OTC gene mutation:
Late-onset phenotype
Patient may be asymptomatic for years and then suffer from a sudden, and sometimes fatal, onset of hyperammonemia

Question 13

3 major IEM groups based on their pathophysiological features

Answer 13

1. Group 1: leading to intoxication
2. Group 2: with energy metabolism defects
3. Group 3: involving complex molecules

Question 14

Typical inheritance pattern of IEMs

Answer 14

Inheritance – mostly autosomal recessive:
o Both father and mother are carriers
o 25% normal baby
o 50% carrier
o 25% affected