Download Document

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
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 )
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