Metabolic disorders presenting as liver disease

A wide range of inherited metabolic disorders lead to biochemical disturbances within the liver. A number of disorders of energy metabolism present as hepatomegaly with hypoglycaemia e.g. glycogen storage diseases or with hypoketotic hypoglycaemia e.g. disorders of fat oxidation. Other defects of carbohydrate metabolism also present with hypoglycaemia and liver disease either in neonates e.g. galactosaemia and fructose-1,6-bisphosphatase deficiency or at weaning i.e. hereditary fructose intolerance. Mitochondrial respiratory chain defects frequently present in neonates/infants as liver disease but often there is other (multi)-organ involvement and persistent lactic acidaemia. Many disorders of peroxisomal and lysosomal metabolism cause a spectrum of liver dysfunction. Urea cycle disorders manifest as hyperammonaemia often presenting acutely in neonates but also in older children and adults. Other causes of liver disease include disorders of copper, bile acid and bilirubin metabolism. Definitive diagnosis requires specialist expertise, however once clinical liver disease is apparent, most disorders are associated with characteristic findings on routine laboratory testing that should raise the suspicion of metabolic disease.