Seizures and stupor during intravenous mannose therapy in a patient with CDG syndrome type 1b (MPI-CDG).
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.
Dr von Hauner's Childrens Hospital, Ludwig-Maximilians-University Munich, Lindwurmstr 4, 80337 Munich, Germany. sebastian.schroeder@med.uni-muenchen.de
A Sebastian
AS
Schroeder
Matthias
M
Kappler
Michaela
M
Bonfert
Ingo
I
Borggraefe
Carola
C
Schoen
Karl
K
Reiter
D000255:Adenosine Triphosphate / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D018981:Congenital Disorders of Glycosylation / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D004569:Electroencephalography; D004734:Energy Metabolism; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008358:Mannose / Q000008:administration & dosage / Q000009:adverse effects*; D008359:Mannose-6-Phosphate Isomerase / Q000172:deficiency* / Q000235:genetics; D010641:Phenotype; D012640:Seizures / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy; D053608:Stupor / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D001786:Blood Glucose; D000255:Adenosine Triphosphate; D008359:Mannose-6-Phosphate Isomerase; D005947:Glucose; D008358:Mannose
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