Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021831 (enteropathy)
 4,403 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CDG-Ib is the "gastro-intestinal" type of the congenital disorders of glycosylation (CDG) and a potentially treatable disorder. It has been described in patients presenting with congenital hepatic fibrosis and protein losing enteropathy. The symptoms result from hypoglycosylation of serum- and other glycoproteins. CDG-Ib is caused by a deficiency of mannose-6-phosphate isomerase (synonym: phosphomannose isomerase, EC 5.3.1.8), due to mutations in the MPI gene. We determined the genomic structure of the MPI gene in order to simplify mutation detection. The gene is composed of 8 exons and spans only 5 kb. Eight (7 novel) different mutations were found in seven patients with a confirmed phosphomannose isomerase deficiency, analyzed in the context of this study: six missense mutations, a splice mutation and one insertion. In the last, the mutation resulted in an unstable transcript, and was hardly detectable at the mRNA level. This emphasizes the importance of mutation analysis at the genomic DNA level.
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PMID:Genomic organization of the human phosphomannose isomerase (MPI) gene and mutation analysis in patients with congenital disorders of glycosylation type Ib (CDG-Ib). 1098 May 31

An Asian girl presented with failure to thrive, congenital hepatic fibrosis, protein losing enteropathy, and hypoglycaemia. Phosphomannose isomerase activity in skin fibroblasts was reduced. She is homozygous for a mutation, D131N, in the phosphomannose isomerase gene (PM1), consistent with the diagnosis of carbohydrate deficient glycoprotein syndrome type 1b. She responded to oral mannose treatment.
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PMID:Successful treatment of carbohydrate deficient glycoprotein syndrome type 1b with oral mannose. 1156 48

Congenital disorders of glycosylation (CDG) are recessively inherited multisystemic disorders resulting from several genetic defects affecting the assembly, transfer or processing of oligosaccharides onto proteins and other glycoconjugates. CDG type Ib is due to a deficiency of phosphomannose isomerase (PMI) encoded by the MPI gene. PMI catalyzes the interconversion of fructose-6-P and mannose-6-P. The clinical phenotype is characterized by gastro-intestinal and hepatic symptoms. In contrast to most CDG patients, there is no neurological affectation. It's a mannose treatable disorder. We report the first recognised case of CDG Ib in Spain. He presented at 6 months with hypoglycaemia, failure to thrive and hypertransaminasaemia. He subsequently developed an enteropathy with subtotal villous atrophy on biopsy. The %CDT was very high and he presented with a type 1 pattern in transferrin isoelectric focusing. PMI activity in fibroblasts was very deficient. Mutations in MPI gene at R219Q and R56fs were found. Clinical and biochemical parameters normalised after treatment with mannose 1 g/kg/day in 5 doses. CDG Ib should be considered in patients with hypoglycaemia, liver disease, enteropathy and hypercoagulability, in the absence of other common causes, and particularly if some of them are combined.
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PMID:[Congenital disorder of glycosylation type 1b. Experience with mannose treatment]. 1892 5

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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PMID:Seizures and stupor during intravenous mannose therapy in a patient with CDG syndrome type 1b (MPI-CDG). 2124 Jun 68

The mannose phosphate isomerase-congenital disorder of glycosylation (MPI-CDG) is caused by phosphomannose isomerase deficiency. Clinical features include hyperinsulinaemic hypoglycaemia, protein losing enteropathy, hepatomegaly and hepatic fibrosis, digestive symptoms and coagulation abnormalities. The condition is treated with mannose supplementation. Long-term outcomes in adults are not well described. We present a case of an adult female patient who discontinued mannose therapy in her adolescence. In adulthood she developed gastrointestinal problems, chronic anaemia and osteophytes in her knees.
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PMID:Clinical outcomes in an adult patient with mannose phosphate isomerase-congenital disorder of glycosylation who discontinued mannose therapy. 3296 65