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Erschienen in: Journal of Inherited Metabolic Disease 3/2010

01.12.2010 | Case Report

Seizures and stupor during intravenous mannose therapy in a patient with CDG syndrome type 1b (MPI-CDG)

verfasst von: A. Sebastian Schroeder, Matthias Kappler, Michaela Bonfert, Ingo Borggraefe, Carola Schoen, Karl Reiter

Erschienen in: Journal of Inherited Metabolic Disease | Sonderheft 3/2010

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Abstract

MPI-CDG (formally called CDG 1b), caused by phosphomannose isomerase (MPI) deficiency, leads to hypoglycaemia, protein losing enteropathy, hepatopathy, and thrombotic events, whereas neurologic development remains unaffected. Dietary supplementation of mannose can reverse clinical symptoms by entering the N-glycosylation pathway downstream of MPI. When oral intake of mannose in patients with MPI-CDG is not possible, e.g. due to surgery, mannose has to be given intravenously. We report a patient with MPI-CDG on intravenous mannose therapy that showed severe depression of consciousness and seizures without apparent cause. EEG and cranial MRI findings were compatible with metabolic coma whereas extended laboratory examinations including repeated blood glucose measurements were normal. Importantly, an intravenous bolus of glucose immediately led to clinical recovery and EEG improvement. Mannose did not interfere with glucose measurement in our assay. We suggest that in patients with MPI-CDG, intravenous mannose infusion can lead to intracellular ATP deprivation due to several mechanisms: (1) in MPI deficiency, mannose 6-P cannot be isomerised to fructose 6-P and therefore is unavailable for glycolysis; (2) animal data has shown that accumulating intracellular mannose 6-P inhibits glycolysis; and (3) elevated intracellular mannose 6-P may induce an ATP wasting cycle of dephosphorylation and rephosphorylation (“honey bee effect”). The mannose-induced metabolic inhibition may be overcome by high-dose glucose treatment. We caution that, in patients with MPI-CDG, life-threatening central nervous system disturbances may occur with intravenous mannose treatment. These may be due to intracellular energy failure. Clinical symptoms of energy deficiency should be treated early and aggressively with intravenous glucose regardless of blood glucose levels.
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Metadaten
Titel
Seizures and stupor during intravenous mannose therapy in a patient with CDG syndrome type 1b (MPI-CDG)
verfasst von
A. Sebastian Schroeder
Matthias Kappler
Michaela Bonfert
Ingo Borggraefe
Carola Schoen
Karl Reiter
Publikationsdatum
01.12.2010
Verlag
Springer Netherlands
Erschienen in
Journal of Inherited Metabolic Disease / Ausgabe Sonderheft 3/2010
Print ISSN: 0141-8955
Elektronische ISSN: 1573-2665
DOI
https://doi.org/10.1007/s10545-010-9252-x

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