MANGANESE TOXICITY IN CHILDREN RECEIVING LONG-TERM PARENTERAL-NUTRITION

Background In patients receiving long-term parenteral nutrition (PN), cholestatic disease acid nervous system disorders have been associated with high blood concentrations of manganese. In such patients, the no rmal homoeostatic mechanisms of the liver and gut ate bypassed and the requirement for this trace element is not known; nor has it been cert ain whether hypermanganesaemia causes the cholestasis or vice versa. W e explored the direction of effect by serial tests of liver function a fter withdrawal of manganese supplements from children receiving long- term PN. We also examined the relation between blood manganese concent rations and brain lesions, as indicated by clinical examination and ma gnetic resonance imaging (MRI). Methods From a combined group of 57 ch ildren receiving PN we identified 11 with the combination of hypermang anesaemia and cholestasis; one also had a movement disorder. Manganese supplements were reduced in the first three and withdrawn in the rema inder. MRI was done in two of these children. We also looked at mangan ese concentrations and MRI scans in six children who had received PN f or more than 2 years without developing liver disease. Findings In the hypermanganesaemia/cholestasis group, four of the 11 patients died. I n the seven survivors baseline whole-blood manganese was 615-1840 nmol /L, and after 4 months it had declined by a median of 643 nmol/L (p<0 . 01). Over the same interval total bilirubin declined by a median of 70 mu mol/L (p<0 . 05). Two of these children had movement disorders, one of whom survived to have an MRI scan; this showed, with T1 weighte d images, bilateral symmetrically increased signal intensity in the gl obus pallidus and subthalamic nuclei. Such changes were also seen in f ive other children-one from the hypermanganesaemia/cholestasis group a nd four of six in the long-term PN group without liver disease (in all of whom blood manganese was above normal). Interpretation The cholest asis complicating PN is multifactorial, but these results add to the e vidence that manganese contributes. In view of the additional hazard o f basal ganglia damage from high manganese levels in children receivin g long-term PN, we recommend a low dose regimen of not more than 0 . 0 18 mu mol/kg per 24 h together with regular examination of the nervous system.