Disorders of galactose, pentose, and pyruvate metabolism

Abstract Inborn errors of galactose metabolism—galactose is principally found as free lactose in dairy products. Three inborn errors of galactose metabolism are recognized: (1) galactokinase deficiency (‘galactose diabetes’)—a very rare condition which impairs the assimilation of dietary galactose such that the free sugar and its metabolites appear in plasma and urine; (2) classical galactosaemia (galactose-1-phosphate uridylyltransferase deficiency)—the commonest (1/47 000 births) and most important disorder. High concentrations of galactose in the plasma and tissues lead to aberrant glycosylation of glycoproteins and other glycoconjugates, including lipids. The principal manifestations are a bactericidal defect associated with neonatal Escherichia coli sepsis; failure to thrive; and—in older patients—growth retardation, mental retardation, renal Fanconi’s syndrome, jaundice, and hepatosplenomegaly: without exclusion of lactose and galactose, death with cirrhosis is the rule. (3) Uridine diphosphate galactose-4´-epimerase deficiency—a rare but often harmless disorder which may be identified by neonatal screening. Rarely, cataract, sensorineural deafness and impaired psychomotor development with hepatorenal features of classical galactosaemia occur, with favourable responses to the galactose exclusion diet. Pentosuria—essential pentosuria is an asymptomatic, autosomal recessive trait affecting glucuronate metabolism, principally found in Ashkenazi Jews. Disorders of pyruvate metabolism—deficiency of the pyruvate dehydrogenase complex is the most common inherited disorder with lactic acidaemia, most often due to deficiency of the E1α subunit inherited as a dominant X-linked character. Presentation is with overwhelming neonatal acidosis; moderate lactic acidosis with progressive neurological features; or—in male children and young adults—an indolent neurological course without overt acidosis but with episodes of cerebellar ataxia induced by carbohydrate administration. Pyruvate carboxylase deficiency causes lactate/pyruvate acidosis with a necrotizing encephalopathy resembling Wernicke’s encephalopathy. Hypoglycaemia may complicate intercurrent infections and starvation.