Hypermanganesemia in Children With Liver and Portosystemic Circulation Disorders: A Systematic Review

AIM: Children with chronic liver disease and portosystemic circulation disorders may have long-term neurocognitive problems. Hypermanganesemia, reported in this group, could be a contributor. This systematic review aimed to characterise liver and portosystemic circulation disorders associated with hypermanganesemia and reported neurocognitive outcomes. METHODS: MEDLINE, PubMed and Embase were systematically searched from inception to February 2023. Study quality and risk of bias were assessed using the Joanna Briggs Institute (JBI) critical appraisal tools and the Navigation Guide framework, respectively. RESULTS: Eighteen studies (n = 103 patients) were included. Seventy of 103 had evidence of hypermanganesemia-47/78 with chronic liver disease and 23/25 with portosystemic shunts without liver disease. Among these, 40/70 had elevated manganese levels, 60/70 had characteristic MRI changes and 30/70 had both. Manganese levels and MRI abnormalities normalised in most cases following definitive treatment of chronic liver disease and portosystemic shunting. Neurocognitive outcomes were inconsistently reported. CONCLUSIONS: Portosystemic shunting is likely an important risk factor for hypermanganesemia in children with liver and portosystemic circulation disorders. Substantial gaps and biases limit firm conclusions about its independent contribution to neurocognitive outcomes, highlighting the need for a structured framework including shunt status, biochemical markers including manganese and longitudinal neurocognitive profiling.