Metabolic disorders

  • See also

    Afebrile seizures
    Recognition of the seriously unwell neonate and infant

    Key points

    1. Metabolic disorders present at all ages with a variety of symptoms and signs that mimic common childhood illness. A high index of suspicion is needed to make a diagnosis
    2. Consider a metabolic disorder in any newborn with unexplained encephalopathy or progressive illness, particularly following an uncomplicated pregnancy and birth
    3. Once suspected, consult the metabolic team urgently
    4. Collection of appropriate urine and blood samples during an acute illness is the key to diagnosis, but should not delay management


    • Metabolic disorders are a large group of inherited conditions resulting from a block (partial or complete) to a pathway in the body’s metabolism, or defects in the transport of substances
    • Though individually rare, collectively they represent an important cause of childhood morbidity and mortality
    • Newborn screening will diagnose many but not all metabolic disorders. A newborn may also become unwell before results are available
    • Diagnosis and management should always involve close liaison with a metabolic team


    Acute presentations where a metabolic disorder should be considered

    • Confusion or lethargy that may progress to coma, without clear evidence of injury, intoxication or other neurological event
    • Newborn with poor feeding, weak suck or hypotonia, often after asymptomatic period
    • Recurrent seizures
    • Presumed sepsis with poor response to treatment
    • Unexplained shock or cardiac failure
    • Rapid, deep breathing +/- progression to apnoea
    • Infant with Brief Resolved Unexplained Event (especially if recurrent)
    • Unexpected blood gas derangement (metabolic acidosis, respiratory alkalosis or hypoglycaemia)
    • Liver dysfunction, hepatomegaly or splenomegaly
    • Any acute presentation with multisystem involvement


    • Family history (a pre-existing family history is uncommon)
      • parental consanguinity
      • unexplained paediatric death (especially neonatal males)
      • relatives with similar presentations or unexplained neurodevelopmental disorders
    • Pregnancy and antenatal history
      • illness in pregnancy
      • diet including vegetarian/vegan diet and hyperemesis
      • HELLP syndrome (foetus may have a fatty acid oxidation disorder)
      • acute fatty liver of pregnancy
    • Neonatal period:
      • suspected sepsis without evidence of infection
      • lethargy, poor feeding/weak suck
      • vomiting, weight loss
      • respiratory compromise, apnoea
      • hypotonia
      • progressive encephalopathy 
      • seizures
      • liver dysfunction
    • Progression of symptoms across childhood:
      • developmental delay or regression
      • recurrent unexplained vomiting
      • recurrent illness precipitated by catabolic episodes (infection, exercise, fasting) or certain foods or medicines
      • aversion to certain foods eg protein, fruit
      • unexplained neurological symptoms (behavioural changes, encephalopathy, seizures, ataxia)
      • unexplained exercise intolerance (myalgia, rhabdomyolysis)
      • acquired hepatomegaly and/or splenomegaly


    • Facial dysmorphism or coarsening of features
    • Lethargy
    • Hypotonia
    • Altered conscious state or encephalopathy
    • Dehydration
    • Jaundice
    • Hepatosplenomegaly
    • Tachypnoea, apnoea
    • Cardiac failure
    • Ocular changes (cataracts, retinal changes, optic atrophy, strabismus)
    • Unusual body odour eg maple syrup in MSUD, sweaty feet in isovaleric aciduria
    • Skin eg xanthomas, nodules, kinky hair, rash
    • Growth parameters

    Interpretation of clinical findings should always be made in consultation with a metabolic team



    Metabolites indicative of metabolic disorders are best detected at time of acute presentation

    Careful collection and handling of blood, urine and CSF samples is important, but should not delay management of the unwell child

    First line investigations (collection as per local hospital protocol)

    • Blood:
      • venous or capillary blood gas
      • glucose (point of care testing appropriate)
      • serum lactate (venous sample)
      • serum ammonia (transfer sample urgently)
      • other tests as clinically indicated eg FBC, UEC, LFT, CRP, cultures
    • Urine
      • ketones, glucose, pH
      • metabolic screen (including ammino acids and organic acids)

    Interpretation of first-line investigations:

    • Interpretation must take account of the clinical context - unwell children without an underlying metabolic disorder frequently have deranged blood gas values
    • Consult the metabolic team urgently to discuss abnormal results
    • The acid-base state, glucose levels, ketones and ammonia may help to classify the type of metabolic disorder (see table in additional notes)
    • Hyperammonaemia is a medical emergency

    Second line investigations

    • As advised by metabolic team


    Principles of management
    These apply to the unwell child with a suspected metabolic disorder, and for subsequent presentations where a diagnosis is already known

    Children with a known metabolic disorder will likely have their own emergency management plan

    • Resuscitation
    • Early consultation with metabolic team
      • as soon as a metabolic disorder is suspected
      • for children who present with a known metabolic condition, access the child’s emergency management plan
    • Stop intake of any triggering factors
      •  eg stop feeds
    • Maintain hydration
      • use intravenous or nasogastric fluids to correct dehydration and replace ongoing losses eg vomiting, diarrhoea
    • Prevent catabolism
      • intravenous fluids such as glucose 10% with sodium chloride 0.9% is standard first-line treatment for an unwell child with a metabolic disorder, except for mitochondrial conditions (these require glucose 5% with sodium chloride 0.9%)
      • special metabolic formula or additional IV lipids/nutrition may be required after discussion with the metabolic team  
    • Enhance disposal of toxic metabolites
      • intravenous medications to chelate or divert toxic metabolites, or replenish deficient metabolites, depending on metabolic disorder in consultation with the metabolic team
      • haemofiltration in ICU may be required if there is a rapid deterioration due to accumulation of toxic metabolites

    Peri-operative management of a child with a known or suspected metabolic disorder should:

    • always be planned early with the metabolic team
    • generally avoid prolonged fasting with provision of sufficient calories (using IV glucose-containing solutions) to prevent catabolism

    Consider consultation with local paediatric team when

    Any child with a suspected metabolic disease

    Consider transfer when

    A child requiring care beyond the comfort level of the hospital
    For emergency advice and paediatric or neonatal ICU transfers, see Retrieval Services

    Consider discharge when

    Following discussion with local metabolic service

    Additional notes

    Interpretation of initial investigations

    • Serves as a guide only: consult the metabolic team with abnormal results
    • Table below is most relevant for neonates and small infants
    • Must also take account of the clinical context, including the period of fasting prior, hydration status, stage of illness and what fluids or other management have already been started
    • An unwell child without a metabolic disorder may have lactic acidosis, respiratory alkalosis hypoglycaemia and ketonaemia 

    Metabolic condition



    Metabolic acidosis


    Anion Gap2

    Urine ketones

    Maple Syrup Urine Disease

    Low or Normal


    Variably present


    May be increased


    Organic Acidurias

    Low or Normal

    May be high

    Very acidotic

    May be high

    Usually increased


    Fatty Acid Oxidation Disorders

    Low or Normal

    May be high

    Variably present

    May be high

    May be increased

    Negative or low1

    Urea Cycle Disorders

    * Tachypnoeic infant w resp alkalosis



    Early, respiratory alkalosis

    Late, metabolic acidosis

    May be normal




    1 Inappropriately low
    2 Calculate by using (Na) – (Cl + HCO3). Normal 8 to 16 mmol/L

    Additional Resources

    Last updated June 2022

  • Reference List

    1. Bhattacharya K, Moore F, Christodoulou J Genetic Metabolic Disease Chapter 11 in Khong, YT., Malcomson, RDG Keeling’s Textbook of Fetal and Neonatal Pathology 6th edition. 2022. Springer. UK.
    2. Hoffmann, G. 2017. Inherited Metabolic Diseases, 2nd edition, Springer-Verlag. Berlin.
    3. Lee J, Peters H, Metabolic Medicine, Chapter 15, in Harding K, Mason DS, Efron D, Paediatric Handbook, 10th edition. 2021. Wiley-Blackwell. London.
    4. Saudubray, J. 2016. Inborn Metabolic Diseases Diagnosis and Treatment, 6th edition. Springer. UK.
    5. Sutton R V. Metabolic emergencies in suspected inborn errors of metabolism: Presentation, evaluation, and management. UpToDate (viewed 28 July 2021).
    6. Zschocke, J. 2020. Vademecum Metabolicum, 5th edition. Thieme.  Germany.