PAEDIATRIC REFERENCE INTERVALS: COPPER, ZINC AND SELENIUM

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PAEDIATRIC REFERENCE INTERVALS COPPER, ZINC AND
SELENIUM

• Tina Yen, Robert McQuilty, Peter Stewart and John
  Coakley
• Clinical Biochemistry Dept. at PaLMS Royal North
  Shore Hospital, Royal Prince Alfred Hospital and
  Chlidrens Hospital Westmead

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PAEDIATRIC FACTORS
1. pre-term, low birth weight 2. inherited
disorders 3. diet and nutrition 4. malnutrition,
low protein states 5. scarcity of reference
interval studies
fewer samples smaller volumes ethical
implications under-reported due to lack of
sufficient subjects
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ADVANTAGES OF ICP-MS
1. favourable detection limits 0.01 0.1
ug/L 2. simple sample preparation 3. high
throughput 4. ability to measure gt 1
element 5. sample volume small 6. ability to
measure isotopes
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TRACE ELEMENT STUDIES

• monitoring essential trace elements in TPN, home
  TPN
• 2. overdose, poisoning
• 3. treatment of toxicity, use of chelation Rx
• eg. oral zinc therapy --gt copper deficiency

incidence 16 in patients intravenously fed for
period longer than 2 wk
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USE OF TPN

• short bowel syndrome of infancy
• intestinal fistula
• cancer cachexia
• radiation enteropathy
• severe postoperative stricture following
  esophago-gastric resection
• situations where protein intake is restricted,
  eg. PKU and maple syrup urine disease

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DEFICIENCY STATES
inherited
SELENIUM
ZINC
COPPER
juvenile cardiomyopathy Keshan disease
chondrodystrophy Kaschin-Beck disease
acrodermatitis enteropathica
Menkes syn
acquired
nutritional deficiency TPN
Nutritional protein-restricted diets PKU or
maple syrup urine
self-treatment by ingestion copper-chelating
agents excess oral zinc therapy causing
symptomatic copper deficiency
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DEFICIENCY STATES-2
SELENIUM
ZINC
COPPER
juvenile cardiomyopathy chondrodystrophy
acrodermatitis enteropathica
Menkes syn
Clinical presentation of nutritional deficiencies
anaemia, neutropaenia rarely thrombocytopaenia S
ideroblastic changes or nuclear maturation
defects in erythroid precursors
adults develop eczematoid- dermatitis around
face, nasolabial folds, chin and perineum.
Leg muscle pain and altered serum transaminase
and creatine kinase activities fingernail bed
abnormalities
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TOXIC STATES
SELENIUM
ZINC
COPPER

• ingestion of food or
• beverages contaminated
• by copper
• accidental or deliberate
• ingestion copper salts
• Wilson's disease
• haemolysis
• gastrointestinal injury
• jaundice
• liver failure

acute or chronic toxicity skin and hair
abnormalities gastrointestinal neurological
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EXCLUSION CRITERIA

• 1. severe illness
• 2. laboratory results
• 3. accessory laboratory requests
• 4. additional analysis

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REF INTERVAL STUDY

• ethics
• number of reference subjects
• outliers
• acute phase responses
• APR causes elevated plasma copper, reduction in
  zinc and reduction in selenium
• partitioning

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COPPER

Soldin S. (ed). 2003 0 5 days
1.4 7.2 1 5 years 12.6
23.6 6 9 years 13.2 21.4 10 14
years 12.6 19.0 15 19 years
10.1 18.4
RPAH adult range (ICP-MS) 12 - 22 umol/L
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ZINC
Soldin S. (ed). 2003 0 5 days
9.9 21.4 1 5 years 10.3
18.1 6 9 years 11.8 16.4 10 14
years 11.6 15.4 15 19 years
9.8 15.4
RPAH adult range (ICP-MS) 10 - 18 umol/L
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SELENIUM
Soldin S. (ed). 2003 0 5 days
0.72 1.2 1 5 years 1.22
1.82 6 9 years 1.29 2.05 10 14
years 1.31 2.35 15 19 years
1.31 2.35
RPAH adult range (ICP-MS) 0.75 - 1.35 umol/L
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CONCLUSION

• Until now, paediatric reference intervals have
  used AAS. This study provides the first
  Australian paediatric reference intervals using
  ICP-MS
• Study performed in 2003-2004 and reflects
  characteristics of metropolitan Sydney
• the reference population was defined by absence
  of an acute phase response
• Therefore the reference interval can be used for
  interpreting plasma copper, zinc and selenium
  levels in patients after verifying absence of
  acute phase reaction