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Metabolic Disorders

  • See also:  Hypoglycaemia
    Seizures
    Resuscitation

    Background

    • Metabolic disorders or inborn errors of metabolism (IEM) result from a block (partial or complete) to an essential pathway in the body's metabolism. There are a large number of conditions included in this group of disorders.
    • Management of metabolic disorders can be very complicated and should always involve close liaison with a metabolic physician.
    • Most of these disorders are inherited as autosomal recessive.
    • Many metabolic disorders present in the newborn period or shortly thereafter. Patients may present later, for example during intercurrent illnesses.
    • High index of suspicion required to make diagnosis as the clinical presentation of most metabolic disorders is non-specific.

    History

    • Parental history- consanguineous parents, previous unexplained neonatal deaths or Sudden Infant Death Syndrome (SIDS), family history (e.g. relatives with undiagnosed 'syndrome'), ethnic group (certain diseases only)  
       
    • A metabolic disorder may present differently depending on the age of the child: 
      • Neonatal period: 
        • poor feeding/suck or vomiting
        • hypotonia
        • respiratory compromise/apnoea
        • progressive encephalopathy and seizures
        • clinical picture often mistaken for sepsis
      • Childhood: 
        • recurrent unexplained vomiting with severe dehydration
        • stroke like episodes 
        • acute liver or renal failure
        • cardiomyopathy
        • unexplained encephalopathy and seizures
           
    • Presentation may also be more insidious:
      • Developmental delay or regression
      • Coarsening of features and skeletal changes
      • Psychiatric disorders
      • An acute metabolic disturbance following a recent dietary change e.g. introduction of solids,  fasting or following excessive physical activity
      • Food craving or refusal

    Assessment

    Look for

    • CNS Effects - irritability, changes in consciousness, movement disorder, hypotonia, seizures, coma
    • GIT- poor feeding, vomiting/ dehydration, prolonged jaundice 
    • Developmental- motor/cognitive delay or regression
    • Is there a metabolic acidosis?
    • Is there Hypoglycaemia?
    • Is there ketosis?
    • Is there hyperammonaemia?

    Causes

    • General appearance (e.g. Marfanoid habitus in Homocystinuria), unusual odour (e.g. musty in Phenylketonuria (PKU)), ocular involvement (e.g. cherry red spots in Tay Sachs disease), cataracts (e.g. galactosaemia), hepatosplenomegaly (e.g. Hurler syndrome)

    Investigations

    Blood, urine and CSF samples collected at the time of presentation may be diagnostic

    • Blood
      • Acid-base: capillary sample 
      • Glucose and lactate: fluoride oxalate tube, 1ml 
      • Ammonia: heparinized tube (1ml)- immediately to lab on ice
      • Ketones and free fatty acids: fluoride oxalate tube (2 ml) 
      • Electrolytes (including calcium, phosphate, magnesium) plain gel tube (1 ml)
      • Amino acids; heparinised (1 ml sent on dry ice) 
      • Insulin, cortisol, growth hormone: plain gel tube (3-4 ml) 
      • Full blood count and film (EDTA tube 0.25 ml)
      • Blood drops onto a Guthrie test card (for acyl-carnitine profile)
        • Leave to dry in room air. Do not store in a plastic envelope.
      • Blood volumes required in different tubes (total approximately 10mls): 
        • capillary acid-base sample (180ul- fill tube)
        • Fluoride oxalate (grey) tube- 3ml
        • Heparinised (orange) tube-2 ml (on ice)
        • Plain gel (brown) tube- 5 ml total (2ml on dry ice)
        •  EDTA (pink) tube- 0.25 ml
    • Urine
      • Ward test for pH, ketones, protein, glucose, reducing substances 
      • 5-20ml for amino acids and organic acids
    • CSF
      • Glucose, protein, lactate (0.5ml) and  amino acids (0.5ml clear CSF- sent to lab immediately on dry ice)

    Management

    • Acute management as per resuscitation guidelines (ABC) if required See Resuscitation
    • Consult with Metabolic Physician and check ED patient alert system
    • Intravenous or nasogastric tube fluids to correct dehydration and replace ongoing losses (e.g. vomiting, diarrhoea)
    • Ensure adequate amount of calories for age and weight to avoid catabolism (e.g. glucose solution 10%, intralipid etc.)
    • Hypoglycaemia and/or seizures treated as per guidelines See Hypoglycaemia
    • Intravenous medications to chelate or divert toxic metabolites, or replenish deficient metabolites, depending on metabolic problem (e.g. Carnitine, Arginine, Na-Benzoate, vitamins etc)
    • Haemofiltration in ICU may be required if there is a rapid deterioration due to accumulation of toxic metabolites

    Notes

    • The interpretation results of the blood acid-base state, glucose, ketones and ammonia will help classify the type of metabolic disorder.

    Interpretation of laboratory results - RCH Clinical Handbook 7th Edn, 2003, Blackwell Science. Metabolic Conditions (p475)

    Metabolic condition pH GlucoseKetones Ammonia
    Urea cycle defects

     N or arrow up 20px

     N

     N

     arrow up 20px

    Organic acidaemia 

    arrow down 20px

     arrow up , N or arrow down 20px

     N or arrow up

    arrow up 

    Ketolysis defects, MSUD^ 

     N or arrow down 20px

    N or arrow up

    arrow up 20px

    FA oxidation defects 

    N or arrow down 20px

    N or arrow up

    N or arrow down 20px

    N or arrow up

    Hyperinsulinaemia 

     N 

     arrow down double 20px

     N or arrow up

    Pituitary/adrenal deficiency  

     N

    arrow down 20px

    arrow up 

    N = Normal
    ^MSUD= Maple Syrup Urine Disease

    • Seek advice from Metabolic Physician if there is a suspected metabolic disorder or if there is a child with a known metabolic disorder who presents acutely unwell.
    • Death of a child with a suspected metabolic disorder See  Death of a child with a suspected metabolic disorder
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