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Starship Children’s Health Clinical Guideline Note: The electronic version of this guideline is the version currently in use. Any printed version can not be assumed to be current. Please remember to read our disclaimer. METABOLIC DISEASE – GUIDELINES FOR INVESTIGATION The Acutely Sick Child Basic Metabolic Screen Emergency Management of Presumed Metabolic Disease Children Who Die Without a Diagnosis Management Prognosis Conclusion The Acutely Sick Child For any acutely sick child where metabolic disease is part of the differential diagnosis Obtain bloods BEFORE you commence treatment. Note - you will get the best out of these tests if you contact the laboratory when you suspect metabolic disease. Some of these tests have long turnaround times - if you don’t tell the lab you have a problem they can’t do the tests urgently for you. From the Auckland site, for all the tests, Claire de Luen ( National Testing Centre) , can be contacted on extension 3165 about samples and destination Basic Metabolic Screen Blood: Glucose Gases U&E , LFT’s Ketones ( -Hydroxybutyrate, acetoacetate) Lactate Pyruvate Ammonia Urine: Ketones (-Hydroxybutyrate, acetoacetate) Organic acids screen Amino acid screen Consider: Carnitine, Alanine, Free Fatty Acids Ask the lab not to discard specimens until you have an alternative diagnosis. Lactate, ammonia and pyruvate should be taken from free flowing , non tourniquet blood and analysed stat (on ice). Lactate: Grey top (Fluoride tube), 0.5 ml minimum, All other tests need Green top ( Lithium Heparin) 2 - 5 mls . If hypoglycaemia is prominent, check growth hormone, insulin and cortisol. Carnitine needs to be both free and ester/free ratio. Phone and discuss with lab and send to Sydney, Australia ( cardiomyopathy, organic acidemias, FAODs) Free fatty acids. Performed in Sydney (FAODs) Author: Editor: Drs C Wilson, W Cutfield, J Christodolou Dr Raewyn Gavin Metabolic Disease – Guidelines for Investigation Service: Date Issued: Metabolic Service, Endocrinology 2001 Page: 1 of 4 Starship Children’s Health Clinical Guideline Note: The electronic version of this guideline is the version currently in use. Any printed version can not be assumed to be current. Please remember to read our disclaimer. METABOLIC DISEASE – GUIDELINES FOR INVESTIGATION Organic Acids: Discuss with laboratory. Basic screen performed in N.Z. Often samples need to be sent to Australia. Amino Acids: Quantitative screen performed on plasma after discussion with Dr Dianne Webster, National Testing Centre. If serum ammonia high check urinary orotic acid and plasma amino acids. Emergency Management of Presumed Metabolic Disease General Contact expert help early (see Scriver p1215) Treat hypoxia, infection, dehydration vigorously. Fluids: 150 -175% of maintenance Carbohydrate: 150% maintenance fluids with 10 -15% dextrose concentration. Aim to be anabolic. Note that infants with pyruvate dehydrogenase deficiency, or a defect in the electron transport chain, worsen with a high carbohydrate load. Lipid: 2 - 3 g /kg/day (not in suspected fatty acid oxidation defect) Amino acids: to meet minimal RDA (monitor amino acids)metabolic disease, Guidelines for investigating Acidosis: Severe metabolic acidosis in neonatal period is often fatal. Consider NaHCO3 when HCO3 <15. May need huge amounts in organic acidemias ( beware hyperammonaemia) Vitamins Megadoses of vitamin co-factors are recommended by some Thiamine B1 50 -150mg/day (MSUD, PDH) Cobalamin B12 1 - 2 mg/day (MMA) Biotin 10 - 20 mg/day ( Propionic aciduria ,multiple carboxylase) Riboflavin 20 - 40mg/kg Coenzyme Q 4 mg/kg ( Resp. chain) Carnitine 100-200 mg/kg (FAODs, organic acidemias, urea cycle disorders) Vitamin C 250 -1000mg/kg Vitamin B6 (pyridoxine dependent convulsions) Author: Editor: Drs C Wilson, W Cutfield, J Christodolou Dr Raewyn Gavin Metabolic Disease – Guidelines for Investigation Service: Date Issued: Metabolic Service, Endocrinology 2001 Page: 2 of 4 Starship Children’s Health Clinical Guideline Note: The electronic version of this guideline is the version currently in use. Any printed version can not be assumed to be current. Please remember to read our disclaimer. METABOLIC DISEASE – GUIDELINES FOR INVESTIGATION Hyperammonemia: Sodium benzoate, Sodium phenylacetate or Sodium phenylbutyrate: 250mg/kg loading dose (over 90 minutes) then 250 mg/kg /day slow infusion. (Dr Bobby Tsang, Whangarei, has a patient with OTC, and the only supply of this medication in NZ) Intravenous L-carnitine 100 -200 mg/kg/day L -arginine 400mg/kg/day (or citrulline) Consider testosterone / growth hormone / insulin infusion (0.2-0.3 u/kg/hr) (decrease catabolism) Early consideration of peritoneal / hemo dialysis. Peritoneal dialysis: 40 - 50 ml/kg dialysate via peritoneal catheter, one hour cycles for 24 - 36 hrs. Careful fluid balance, blood glucose, electrolyte measurements. Hemodialyse all neonatal patients with severe hyperammonemia (plasma levels > 10 times normal). Hypoglycaemia See separate guidelines on hypoglycaemia Children Who Die Without a Diagnosis Sudden Infant Death Syndrome (SIDS) Low incidence of metabolic disease, approximately 1 to 3%. (This presumes that it is a true SIDS, i.e. the infant was completely well prior to death). The tests listed below are therefore not generally warranted in SIDS. Consider sending a Guthrie card for Tandem Mass Spectrometry. Other children who die without a diagnosis: Blood (cardiac if not otherwise available ) on filter paper Blood (separate if possible and freeze red cells and plasma separately) - as soon as possible post-mortem. Bile: freeze Urine: freeze Skin biopsy ; fibroblast line. Liver / kidney / muscle: ( small sugar cube size. Wrap in tinfoil and snap freeze to minus 70C, using liquid nitrogen or dry ice if possible. Samples are best taken as soon after death as possible. Consider a needle biopsy if it might take some time to get the samples ) Author: Editor: Drs C Wilson, W Cutfield, J Christodolou Dr Raewyn Gavin Metabolic Disease – Guidelines for Investigation Service: Date Issued: Metabolic Service, Endocrinology 2001 Page: 3 of 4 Starship Children’s Health Clinical Guideline Note: The electronic version of this guideline is the version currently in use. Any printed version can not be assumed to be current. Please remember to read our disclaimer. METABOLIC DISEASE – GUIDELINES FOR INVESTIGATION Hold samples. Await histology. Remember to ask for fat stains as important indicators of metabolic disease (e.g. fatty acid oxidation defects). Remember Guthrie cards are kept by National Testing Centre for organic acid analysis etc (via Tandem Mass Spectrometry). It is also possible to do DNA studies (for MCAD, for example) when a likely diagnosis is found. References 1. Sriver CR et al. The metabolic and molecular basis of inherited disease. Seventh edition. McGraw- Hill, Inc. Health Professions Division. New York. 2. Fernandes J et al. Inborn Metabolic Diseases. Spinger 1996. 3. Buist NRM. Professor of Paediatrics and Molecular and Medical Genetics, Oregan Health Sciences University. Personal communication. 4. Christodoulou J. Senior Lecturer and Clinical Geneticist , New Childrens Hospital, Sydney. Personal communication. Author: Editor: Drs C Wilson, W Cutfield, J Christodolou Dr Raewyn Gavin Metabolic Disease – Guidelines for Investigation Service: Date Issued: Metabolic Service, Endocrinology 2001 Page: 4 of 4