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

Author:Drs C Wilson, W Cutfield, J ChristodolouService:Metabolic Service, Endocrinology

Editor:Dr Raewyn GavinDate Issued:2001

Metabolic Disease – Guidelines for InvestigationPage:1 of 5

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: / Urine:
Glucose / Ketones (-Hydroxybutyrate, acetoacetate)
Gases / Organic acids screen
U&E , LFT’s / Amino acid screen
Ketones ( -Hydroxybutyrate, acetoacetate)
Lactate
Pyruvate
Ammonia
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)
  • 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)

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 70C, 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 )

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.
  1. Fernandes J et al. Inborn Metabolic Diseases. Spinger 1996.
  1. Buist NRM. Professor of Paediatrics and Molecular and Medical Genetics, OreganHealthSciencesUniversity. Personal communication.
  1. Christodoulou J. Senior Lecturer and Clinical Geneticist , New ChildrensHospital, Sydney. Personal communication.

Author:Drs C Wilson, W Cutfield, J ChristodolouService:Metabolic Service, Endocrinology

Editor:Dr Raewyn GavinDate Issued:2001

Metabolic Disease – Guidelines for InvestigationPage:1 of 5