Metabolic Diseases
Background
Some metabolic diseases present throughout the life span from infancy to
adulthood with signs or symptoms of hepatic dysfunction including:
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Hepatomegaly
Jaundice
Hypoglycaemia
Elevation of hepatic enzymes
Hyperammonaemia
Failure to thrive
Protein or food intolerance
Anorexia, vomiting and diarrhoea
Adverse affects of hepatic dysfunction on the central nervous system include
ataxia, stupor, coma and hypoglycaemic episodes.
Examples of in born errors with hepatic dysfunction:
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Urea cycle defects
Organic aciduria
Fatty acid oxidation defects
Hepatic glycogen storage diseases
Tyrosinaemia
Transferase deficient galactosaemia
Hereditary fructose intolerance
Wilson’s disease
Various storage disorders
Almost all disorders are autosomal recessive with incidence ranging from 1 in
10,000 to 1 in 500,000.
Some diseases are detected by screening before any signs of symptoms are
present.
Hyperammonaemic states and organic acidurias can occasionally present with
hepatic more than CNS findings.
Differential diagnosis
Precious time can be lost if the diagnosis of an in born error is not considered
and hepatopathy and CNS symptoms are attributed to perinatal insults.
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Infections; TORCH
Toxins
Pancreatitis
Congenital hepatic and bowel duct malformations
Malrotational volvulus
Ketotic hypoglycaemia
Reye syndrome
History
A full history is essential. Important questions would include:
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Is there a family history of death in early infancy or undiagnosed severe
liver disease?
Is there any pattern to the illness?
o Metabolic deterioration to fasting or childhood infection
o Association of symptoms with ingestion of protein, lactose, sucrose
o salicylate and viral infections
o Inability of patient to fast for longer than 8-12 hours
Physical examination
Full examination essential
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Tachypnoea (caused by metabolic acidosis or respiratory alkalosis
Hepatomegaly
Jaundice
CNS findings
Failure to thrive
Investigations
The most useful samples are those taken at the time of admission when
acutely ill, and this opportunity should not be missed. If a non-metabolic
diagnosis is made subsequently, samples for the special bio-chemical tests can
always be discarded.
1. Essential preliminary tests
a) FBC & differential
Coagulation screen
b) Blood gas and acid base status
Bio-chemical profile
Plasma-glucose
Plasma amino acids
Urine must be saved for organic and amino acids (the best sample is the first
urine past at the time of acute admission). Diagnostic abnormalities often
disappear quickly following IV glucose or other resuscitation. A urine bag should
be applied at once and if possible at least 5mls of urine collected and save the
next urine sample past as well.
c) Other tests indicated by the clinical features – see below
2. Hypoglycaemia without obvious cause
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Us & Es, blood gas and acid base status
Liver function tests
Glucose
Insulin
Growth hormone
Cortisol
Amino acids – OH Butyrate, free fatty acids,
Lactate (if hepatomegaly) if possible, take extra 2mls of blood into a
lithium heparin tube, which can be separated and stored for special
tests (e.g. carnitine)
i) Blood spot on Guthrie card for ACE R carnitines spot plasma
ammonium
Urine
First urine should be tested for ketones and stored for organic and amino acid
analysis.
3. Suspected hyperammonaemia
Ammonia is noted usually when the urea cycle defect is a possible diagnosis and
should be measured in any newborn with unexplained lethargy, neurological
disturbances, fits, vomiting or hyperventilation, especially if the baby was well
initially in the first 24-72 hours of life. Significant values generally exceed
150micromol/l.
This is not an exhausted list of tests, further more specialist testing may be
required.
Treatment
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Restore acid base balance
Administer intravenous glucose at 5-9mg/kg per minute to prevent
catabolism
Acute detoxification to protect the CNS/ remove ammonia/may require
haemofiltration or haemodialysis to be done in a specialist unit
Long –term therapy requires a diet deficient in the offending dietary
component, examples of this include: organic acidurias, protein restriction,
high carbohydrate, glycine, carnitine
Urea cycle disorders, protein restrictions, agents that foster waste,
nitrogen removal: Sodium Benzoate and Sodium Phenylbutyrate –
hypoglycaemic disorders; avoidance of fasting, uncooked starch released
carbohydrate over a prolonged period, continuous night feeds by NG tube
Bibliography
Five-minute paediatric consult – Second Addition
Reviewed 2008, next review 2011