Metabolic and endocrine diseases

Introduction: Metabolic disease The term ‘inborn error of metabolism’ was coined by a British physician, Archibald Garrod (1857–1936), in the early twentieth century. Metabolism is carried out by enzymes and if a genetic abnormality affects the function of an enzyme or causes it to be deficient or missing altogether, various disorders can occur. Inborn errors of metabolism can be divided into three major pathophysiological diagnostic groups: Disorders that disrupt the synthesis or catabolism of complex molecules with symptoms that are permanent, progressive, independent of intercurrent events and not related to food intake. These include lysosomal disorders, peroxisomal disorders and disorders of intracellular transport and processing. Disorders that lead to an acute or progressive accumulation of toxic compounds as a result of metabolic block. These include disorders of amino acid metabolism (phenylketonuria (PKU), homocystinuria, maple syrup urine disease), organic acidurias, congenital urea cycle defects and sugar intolerances (galactosaemia). Disorders with symptoms due to a deficiency of energy production or utilisation within the liver, myocardium, muscle or brain. These include congenital lactic acidaemias, fatty acid oxidation defects, gluconeogenesis defects and mitochondrial respiratory chain disorders. The mechanisms for brain damage resulting in intellectual disability (ID) are not well understood and relatively few metabolic conditions cause ID in isolation (Kahler and Fahey, 2003).