Evidence of cataplerosis in a patient with neonatal classical galactosemia presenting as citrin deficiency

Abstract

Classical galactosemia is an autosomal recessive disorder caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase. Undoubtedly, some of the short term complications are linked to the toxic effects of the accumulated abnormal metabolites (galactose-1-phosphate and galactitol). However, the physiopathology of neonatal liver failure remains unclear. We report the case of a 7-week-old girl who was first diagnosed with liver failure, hypoprotidaemia, ascites and generalized edemas. High citrulline (293 micromol/L), on initial plasma amino acid, suggested the diagnosis of citrin deficiency. As the citric acid cycle intermediates were non-detectable (oxoglutarate, succinate and citrate), a cataplerotic state was suspected. As a result, citrate (as an anaplerotic treatment) induced a clear improvement in her liver function. Four weeks later, this patient was switched to a galactose-free formula (as recommended in citrin deficiency with galactosemia) and her pathological status returned to normal. Citrin deficiency was later ruled out by molecular biology studies; then we reintroduced a galactose-containing formula which re-evoked rapidly vomiting, galactose aversion and hepatic cytolysis and the diagnosis of classical galactosemia was established. Our case clearly shows that cataplerosis could play a role in the pathophysiology of the neonatal liver disease observed in classical galactosemia.