Paediatric Clinical

Biochemistry

Dr Stuart J Moat
Consultant Clinical Biochemist
Director Wales Newborn Screening
Laboratory
University Hospital of Wales

Infants and children develop

abnormal biochemistry - rapidly

Acid base
Electrolytes
Glucose
Bilirubin*
Ammonia*
Calcium
Toxicology
FTT
Developmental delay

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 Pre-analytical Considerations

Blood volumes
Term baby ~275mls
Prem 80-120mls
Specimen collection
Heel prick (less traumatic)
Venepuncture (older infants/child)
Urine collection
Haematocrit
<10 days age Hct 60-70% ie plasma yield
low

Analytical Considerations

Analyser
analyser type (random or batch)
small sample volumes
extensive range of chemistries available
STAT capability
trickle feeding whilst processing
liquid level sensing
Chemistries
known chemistry interferences

Post-analytical Considerations

Reference intervals
Age related variation important
factor when interpreting paediatric
results.

Staff expertise

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 Acid Base

Acid Base
Metabolic acidosis
Loss of HCO3 in fluid
Lactic acidosis (Type A & B) & D-lactate
Starvation ketosis post infection
DKA

Poisoning, RTA, IEMs

Anion gap =((Na + K) (HCO3 + Cl)) Normal<17

Case 1
8 Mo Boy PICU
Floppy, drowsy, poor feeding
BM 1.5, urine ketones +++

pH 6.9
HCO3 7.0
AG 32

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 Electrolytes

Electrolytes
Hypernatraemic dehydration
Inadequate intake
Excessive loss H20 GI, urine (DI)

Sodium overload iatrogenic, poisoning

Electrolytes
Hyponatraemia (more common)
Water overload
Rehydration with sodium poor fluids
Renal or cardiac failure
SIADH
Sodium loss
Urine recovery phase post ARF, osmotic
diuresis, adrenal insufficiency (CAH,
addisons, pseudoaldosteronism)

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 Case 2
3 yr old boy Diarrhoea & dehydration

Na 152 K 2.0
Urea 3.5 Cr 70
HCO3 10
Lactate 5.0
Urine ketones ++
AG 20

Case 3
12 day old boy A/E

Na 106 K 6.6
Urea 8.8 Glucose 2.7

17OHP 6000nmol/L
Urine steroid profile CAH 21 OH-
lase

Glucose

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 Glucose - Hypoglycaemia
High glucose utilisation in young child (per Kg
body weight)
Glycogen stores readily depleted (12-14hrs)
Small muscle mass (limited supply of
gluconeogenic precursors)
Vulnerability to hypoglycaemia
Glucose less than 2.6 mmol/l
1 in 500 hospital admissions

Hypoglycaemia - causes
Increased glucose demand
sepsis, pyrexia, large tumour
Reduced supply
Substrate exhausted (prolonged fast)
Metabolic
FAO, Glycogenolysis, galactosaemia,
Endocrine
Hyperinsulinsim, adrenal insufficiency, hypopit

Hypoglycaemia - Investigations
Glucose
3 OH butyrate 2ml Fluoride Oxalate *
Free Fatty Acids

Insulin
Cortisol
3ml Lithium Heparin*
Growth Hormone
Amino Acids
1ml Lithium Heparin or 2-3 blood
Acyl carnitines spots collected on a Guthrie Card*

Urine organic acids

*check with local laboratory for sample types and minimum volumes

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 Case 4
An 8 month old baby girl admitted to A/E,
short history of being drowsy and floppy.
Excessive sweating and un-responsive to
painful stimuli. BM reported to give a very
low reading by the admission nurse.

Na 146 mmol/L K 5.0mmol/L

Urea 12.8mmol/L Creat 58mol/L
CRP <1 AST 68IU/L
Bilirubin 4mol/L Bicarb 5mmol/L
Glucose 0.5mmol/L

Case 4
Further investigations showed that at the
time her plasma free fatty acids were
4.2mmol/L and her -hydroxybutyrate
was 0.3mmol/L.

Bilirubin metabolism

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 Case 5
2 week old girl, referred by GP to A/E,
breast fed & thriving

Bilirubin 174mol/L, dBili <20mol/L

ALT 29, GGT 78, ALP 198, Alb 38
fT4 18pmol/L, TSH 3.1mU/L
Urine reducing substances - negative

Breast milk jaundice

Case 6
4 week old boy, jaundiced since day 1
Bilirubin 354mol/L, dBili 282mol/L,
abnorm LFTs and hepatosplenomegaly

Referred to Paeds Gastro at week 4 of life

Bilirubin 154mol/L, dBili 148mol/L,
ALT 229, GGT 378, ALP 148, Alb 34, Hb 8.9
OAs, AAs NAD
Liver biopsy macrophages +++
Gaucher Disease

Hyperammonaemia

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 Case 7
Female, 2 wks old, poor feeding for last 24 hrs,
floppy, and becoming drowsy. O/E in casualty he
was unconscious.

BGAs pH 7.5; pCO2 2.1kPa; pO2 18kPa.

Ammonia 1850mol/L (ref <40mol/L)

Na 145 K 3.3 Urea 0.6 Creat 55

ALP 436 ALT 25 Bili 18 Alb 38

Urea cycle disorder OTC deficiency

Toxicology

Toxicology: accidental and

potential poisonings
Peak in 2-6 year olds
15-20% of children <5 years can open child
resistant containers!
A/E found with tablets
Paracetamol, salicylate, iron urgently
Child presenting with symptoms
Para/salicylate/iron/ethanol and Tox screen
Deliberate usually older child
Non-accidental poisoning by family member

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 Failure to Thrive

How to Investigate Infant with Failure To Thrive

? clinical history specific signs/symptoms, social issues

e.g. rickets, liver disease, hepatosplenomegaly, normal feeding,

infections

Malabsorption/
Endocrine Metabolic Renal tubular Malnutrition
defects
GH deficiency Galactosaemia Coeliacs
Hypothyroidism Amino Wilsons Cystic fibrosis
Hypopituitarism acid/organic acid Cystinosis Protein-losing
CAH disorder (MSUD, Tubulopathies enteropathy
MMA) Lactase deficiency
Vitamin deficiencies

Laboratory Investigations 1

Blood
Full blood count including Hb, ESR - assess
anaemia, neutropenia
Iron studies
Folate (low in coeliac)
Routine biochemistry including
- U&E, Bone and liver profiles
- CRP
- TFts
- Immunoglobulins TTG
Chromosomal analysis

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 Laboratory Investigations 2
Faeces
Culture, elastase

Urine
Culture, pH (RTA)

Other
CXR, Sweat test

Developmental Delay

Developmental Delay

Developmental delay 1-3% of children <5

years
Delay in 2 or more developmental domains;
gross & fine motor, speech and language,
cognition, personal and social development.

Most common cause chromosomal and

structural brain abnormalities
1-5% of cases with DVD Metabolic (~200
disorders).

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 Laboratory Investigations for DVD

Regression vs delay
Good clinical history
MetBioNet Ix guidelines
Initial biochemical Ix no specific findings
- Blood
CK, FBC, U/E, Bone, LFT, TFTS, Lactate, NH3, Urate,
biotinidase

- Urine
Organic Acids, Glycosoaminoglycans, creatine (males) if 2
affected siblings

Summary
Interpretation of lab results from
paediatric subjects often difficult!

If uncertain refer for further testing/

advice.

UK MetBioNet

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