intercurrent illness or dietary changes• neurodegeneration•multisystem disorders with organ dysfunction.Acute metabolic decompensationNeonatalIn the neonatal period, metabolic disorders can be grouped into those that becomesymptomatic because of:•the accumulation of a toxin, or•an energy deficiency.Those neonates with toxin accumulation are usually well until 2–5 days of age, as theplacenta has usually cleared the toxin in utero. Poor feeding and lethargy are frequentearly symptoms, followed by a decreased conscious state, biochemical disturbances andabnormalities of tone and movement.The neonate with energy deficiency can present at any time from birth with seizures,acidosis, hypertrophic cardiomyopathy, hypotonia and malformations being commonfeatures.The history can be helpful and questions asked should include possible consanguinity,family history of similar presentations, previous neonatal deaths or stillbirths, particularlyon the maternal side (X-linked or mitochondrial inheritance), and dietary exposures suchas galactose (breast or cow’s milk) or fructose (fruit, honey on dummy). Most of thedisorders are due to an enzyme deficiency, and autosomal recessive inheritance is farmore common than X-linked or maternal mitochondrial inheritance.A very useful approach to diagnosis in the newborn period has been devised by
Saudubray et al (see Further Reading) based on the measurement of glucose, ketones,lactate, ammonium and acidosis.Older childrenAcute metabolic presentations in children beyond the neonatal period are normallyprecipitated by a viral illness associated with loss of appetite or vomiting. This causescatabolism and the gluconeogenic, fat and protein catabolic pathways are stressed.Ingestion of large amounts of protein or deliberately fasting (e.g. for surgery) can alsoprecipitate an acute decompensation in some disorders.For all age groups the presentation can be as decreased conscious state,hypoglycaemia, metabolic acidosis or seizures.Decreased conscious stateA decreased conscious state may be the result of:•metabolic encephalopathy• hypoglycaemia• hyperammonaemia•aminoacidopathies, e.g. maple syrup urine disease.Diagnosis of the latter is based on plasma and urine amino acids, which show elevatedbranched chain amino acids: valine, leucine and isoleucine.HyperammonaemiaHyperammonaemia often causes a respiratory alkalosis. The absence of ketosis can beimportant in distinguishing these disorders from the secondary hyperammonaemia ofpatients with an organic acidosis.Findings and possible causes of hyperammonaemia may be:•normal anion gap – high amino acids:•urea cycle disorders, e.g. citrullinaemia, argininaemia, argininosuccinic aciduria•normal anion gap – low/normal amino acids:•urea cycle disorders, e.g. ornithine transcarbamylase (OTC) deficiency, carbamyl phosphate synthetase (CPS) deficiency•lysinuric protein intolerance•transient hyperammonaemia of newborn (premature babies with respiratory distress)•increased anion gap:•liver disease/failure•organic acidaemias, e.g. methylmalonic acidaemia, propionic acidaemia.