General Guidelines

Any sick baby where metabolic disease is part of the differential diagnosis. Please discuss with the consultant acutely - many of the presentations can present rapid demise.
Important - 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 turn-around times - if you don’t tell the lab you have a problem they can’t do the tests urgently for you.
- Auckland site - Claire de Luen (Biochemical Genetics, LabPlus, can be contacted for all the tests re sample and destination Ext 6678).

Blood

Glucose
Gases
U&E
LFT’s
Ketones (β-Hydroxybutyrate, acetoacetate)
Lactate
Acylcarnitine profile (plasma or blood spot on Guthrie card)
Ammonia
Alanine
Free Fatty Acids

Urine

Ketones - β-Hydroxybutyrate, acetoacetate)
Organic acids screen
Amino acid screen
Glycoaminoglycan screen (if lysosomal disorder suspected)

General Notes

Ask the lab not to discard specimens until you have an alternative diagnosis.

Obtain bloods BEFORE treatment is commenced.
Lactate: fluoride tube, grey top 0.5ml minimum
All other tests need green top (Li. Heparin) 2-5 mls.
If hypoglycaemia a prominent feature check growth hormone, insulin and cortisol.
If serum ammonia high check urinary orotic acid and plasma amino acids.

Any child who dies without a diagnosis, SIDS:

Information for post-mortem studies

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 frozen, -70°C, use 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 post-mortem 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 Spec. Also possible to do DNA studies [e.g. MCAD] when a likely diagnosis is found).

Emergency protocol for presumed metabolic disease

General

Contact expert help - Dr Callum Wilson is the local metabolic paediatrician. He can be contacted through the Starship Operator.

Treat hypoxia, infection, dehydration vigorously
Fluids: 150-175%of maintenance
Carbohydrate: maintenance of at 10-16% dextrose (pyruvate dehydrogenase deficiency or electron transport chain defect patients worsen with high carbohydrate load)
Lipid: 2-3 g/kg per day (not in suspected fatty acid oxidation defects)
Amino acids: to meet minimal RDA requirements (monitor amino acids)

Acidosis

Severe metabolic acidosis in neonatal period is often fatal.
Consider sodium bicarbonate when HCO₃ <15. May need huge amounts to correct acidosis in organic acidaemias (beware hyperammonaemia)
Megadoses of vitamin co-factors are recommended by some authors.
- Thiamine B1 50-150mg/day (MSUD,PDH)
- Cobalamin B12 1-2mg/day (MMA)
- Biotin 10-20mg/day (Propionic aciduria, multiple carboxylase)
- Riboflavin 20-40mg/kg
- Coenzyme Q 4mg/kg (Resp. chain)
- Carnitine 100-200mg/kg (FAOD’s organic acidemias, urea cycle)
- Vitamin C 250-1000mg/kg
- Vitamin B6(pyridoxine dependent convulsions)

Hyperammonaemia

Sodium benzoate, Sodium phenylacetate or sodium phenylbutyrate: 250mg/kg loading dose (over 90 minutes) then 250mg/kg /day slow infusion.
IV L-carnitine 100-200mg/kg /day
L-arginine 400mg/kg /day (or citrulline)
Consider testosterone/growth hormone/insulin infusion (0.2-0.3u/kg/hr) (decrease catabolism)
Early consideration of peritoneal dialysis or haemodialysis. Peritoneal dialysis: 40-50ml/kg dialysate via peritoneal catheter, one hour cycles for 24-36 hrs. Careful fluid balance, blood glucose, electrolyte measurements, All neonatal patients with severe hyperammonaemia (plasma levels greater than 10 times normal) should be haemodialysed.
Contact expert help early