1. Audit of reducing sugars requesting Chris Stockdale

2. Reducing sugars A sugar which has an aldehyde group capable of reducing Cu(II)

3. 00.250.50.7512 % reducing sugar Sugar TLC Xylose Glucose Fructose Galactose Sucrose Maltose Lactose

4. Requests from 30/3/11 to 4/5/11 66 faeces requests, 13 urine requests Sugar TLC performed on 56 of these (47 faeces, 9 urines) Analysis of reducing sugars requesting

5. Urinary reducing sugars STM BRHC Other hospitals

6. CauseReducing substances in urine Diabetes mellitusGlucose GalactosaemiaGalactose (glucose) Hereditary fructose intoleranceFructose Essential fructosuria (benign)Fructose Essential pentosuria (benign)L-xylulose AlkaptonuriaHomogentisic acid Fanconi syndromeGlucose, galactose Liver dysfunctionGalactose, fructose Citrin deficiencyGalactose Hereditary tyrosinaemiap-Hydroxyphenylpyruvic acid DrugsSalicylate, levodopa, cephalosporins When do reducing substances appear in urine?

7. GalactosaemiaHereditary fructose intolerance Enzyme affectedGalactose 1 phosphate uridyl transferase (GALT) Aldolase B Incidence1/45k1/20k SymptomsLiver & kidney dysfunction, brain damage, hypoglycaemia Liver & renal tubular dysfunction, hypoglycaemia, avoidance of fructose containing foods OnsetSymptoms in first week of lifeSymptoms upon weaning DiagnosisGALT activity assay RBC galactose-1-phosphate Urine galactose/galactitol DNA analysis Nutritional history DNA analysis

8. Reasons for urine requests Hyperbilirubinaemia/jaundice Hypoglycaemia Renal tubular acidosis Reducing substances testing recommended by Metbionet and/or local guidelines for investigation of: hypoglycaemia conjugated hyperbilirubinaemia early presenting jaundice prolonged jaundice

9. Reducing sugars testing in galactosaemia and HFI False positive results –Other causes of liver dysfunction False negative results –Galactosaemiarecent blood transfusion not on regular milk feed –HFIliterature reports of false negative results ‘although determination of reducing substances in the urine can be used as a first simple screening test for classical galactosaemia, this test should not be used either to confirm or to reject a diagnosis’

10. Action points: urine Test no longer available Clinicians directed to GALT testing when galactosaemia suspected References to test withdrawn from local guideline documents

11. Faecal reducing substances

12. BRHC STM GP Other hospitals Derriford Taunton Weston Cheltenham Bath

13. Faecal reducing substances Why? If sugar malabsorption is suspected Inability to absorb a sugar will lead to its appearance in faeces

14. Lactose malabsorption Clinically the most important form of sugar malabsorption Lactase deficiency Lactose accumulation in small intestine Leads to bloating, pain, flatulence, diarrhoea, FTT, colic Primary, secondary and developmental forms

15. Lactose malabsorption Clinically the most important form of sugar malabsorption Lactase deficiency Lactose accumulation in small intestine Leads to bloating, pain, flatulence, diarrhoea, FTT, colic Primary, secondary and developmental forms

16. Reducing substances testing in diagnosis of lactose intolerance False negative results –Bacterial metabolism of faecal sugars (can be reduced by freezing samples) No significant difference could be established between normal children and children with malabsorption syndromes in terms of faecal pH and sugar chromatography. Schaub & Lentze (1973) Sugars, lactic acid and pH in feces of children. A useful diagnostical approach for gastrointestinal disorders? Eur J Pediatrics, 115, 141-53. ‘fecal reducing sugars can also be measured and become positive by excretion of a reducing sugar in the stools’

17. Alternative tests for diagnosis of lactose intolerance Hydrogen breath test Trial of lactose free diet

18. Action points: faeces Test only available in children up to 16 Requestors alerted to possibility of false negative results Advise freezing of samples from external locations Test no longer performed on fully formed stools Sugar TLC performed only on samples with 0.5% or above reducing substances

19. Reducing substances testing decreased from 79 to 43 ReasonNumber of samples excluded Urine13 Faecal requests on patients >16 4 Fully formed samples20 Total37 ReasonNumber of samples excluded Urine9 Faecal requests on patients >16 4 Fully formed samples11 0.25% reducing substances20 Total44 Sugar TLC testing decreased from 56 to 12 Results of the changes to the availability of these tests

20. Acknowledgements Clinical Biochemistry, BRI –Ann Bowron –Dr Vicki Powers –Dr Janet Stone Bristol Royal Hospital for Children –Dr Christine Spray Metabolic Biochemistry Network –http://www.metbio.net/