Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:5.4.2.8 (phosphomannomutase)
238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In fibroblasts from five patients with carbohydrate-deficient glycoprotein syndrome type 1, the incorporation of [2-3H] mannose into mannose phosphates, GDP-mannose, GDP-fucose, dolichol-P-mannose, lipid-linked oligosaccharides, and glycoprotein fraction was determined. We observed a 3- to 5-fold reduction of incorporation of radioactivity into mannose 1-phosphate, GDP-mannose, GDP-fucose, dolichol-P-mannose, and nascent glycoproteins. The incorporation of radioactivity into mannose 6-phosphate was normal. The formation of lipid linked oligosaccharides was only slightly affected (</=20%), but their size was severely reduced, mostly containing five or fewer residues. As a consequence, truncated oligosaccharides were transferred to newly synthesized glycoproteins. The metabolic changes can be explained by a deficiency of phosphomannomutase activity, which was reduced to </=10% of control.
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PMID:Abnormal synthesis of mannose 1-phosphate derived carbohydrates in carbohydrate-deficient glycoprotein syndrome type I fibroblasts with phosphomannomutase deficiency. 945 Oct 26

Human beta-trace protein is a major intrathecally synthesized polypeptide constituent of human cerebrospinal fluid. We have previously shown that this protein is almost quantitatively modified with biantennary complex-type N-linked oligosaccharides which show "brain-type" glycosylation characteristics (Hoffmann,A. et al., J. Neurochem., 63, pp. 2185-2191, 1994). In the present study human beta-trace protein from the cerebrospinal fluid (CSF) of patients with carbohydrate-deficient glycoprotein syndrome (CDGS) due to phosphomannomutase (PMM) deficiency and N-acetyl-glucosaminyltransferase II (GlcNAc-T II) deficiency as well as from control individuals was studied by Western blot analysis. The protein from pooled CSFs was purified by immunoaffinity chromatography. The protein from the five patients with CDGS PMM deficiency showed three protein bands upon SDS-PAGE analysis corresponding to the di-, mono-, and unglycosylated polypeptide forms. Carbohydrate structural analysis of the enzymatically liberated N-glycans was performed applying mapping by HPAEC-PAD, methylation analysis as well as MALD/TOF-MS. Essentially identical oligosaccharide structures were detected in beta-TP from type I patients and control adult pooled CSF. The beta-trace protein from two patients with GlcNAc-T II deficiency showed a single di-N-glycosylated protein band with a significantly lower molecular weight than the di-glycosylated polypeptide from control patients and the beta-trace protein from pooled adult CSF. Beta-TP from GlcNAc-T II deficiency patients shared only three oligosaccharides out of the 13 observed in beta-TP from controls or patients with PMM deficiency. The major oligosaccharide structures of the glycoprotein from patients with GlcNAc-T II deficiency were found to be monoantennary asialo- or monosialylated lactosamine-type chains with proximal fucose and bisecting GlcNAc.
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PMID:Hypoglycosylation of a brain glycoprotein (beta-trace protein) in CDG syndromes due to phosphomannomutase deficiency and N-acetylglucosaminyl-transferase II deficiency. 945 8

To report the first case of carbohydrate deficient glycoprotein syndrome Type I (CDG I) that has been identified in Australia and confirmed enzymatically to raise the awareness of paediatricians with regard to CDG I and its manifestations, implications and diagnostic investigations. Clinical and autopsy findings of an infant with CDG I are presented. The diagnosis of CDG I was suggested by the clinical findings and biochemical abnormalities and was confirmed by showing an abnormal transferrin isoform pattern. Subsequent studies showed a reduced level of phosphomannomutase in skin fibroblasts. Carbohydrate-deficient glycoprotein syndrome I is one of the many causes of cerebellar hypoplasia. It is an important disorder to identify because of the prognostic and genetic implications and may be underdiagnosed in Australia.
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PMID:Carbohydrate deficient glycoprotein syndrome type I: a cause of cerebellar vermis hypoplasia. 948 87

Carbohydrate-deficient-glycoprotein syndrome type 1 (CDG1; also known as "Jaeken syndrome") is an autosomal recessive disorder characterized by defective glycosylation. Most patients show a deficiency of phosphomannomutase (PMM), the enzyme that converts mannose 6-phosphate to mannose 1-phosphate in the synthesis of GDP-mannose. The disease is linked to chromosome 16p13, and mutations have recently been identified in the PMM2 gene in CDG1 patients with a PMM deficiency (CDG1A). The availability of the genomic sequences of PMM2 allowed us to screen for mutations in 56 CDG1 patients from different geographic origins. By SSCP analysis and by sequencing, we identified 23 different missense mutations and 1 single-base-pair deletion. In total, mutations were found on 99% of the disease chromosomes in CDG1A patients. The R141H substitution is present on 43 of the 112 disease alleles. However, this mutation was never observed in the homozygous state, suggesting that homozygosity for these alterations is incompatible with life. On the other hand, patients were found homozygous for the D65Y and F119L mutations, which must therefore be mild mutations. One particular genotype, R141H/D188G, which is prevalent in Belgium and the Netherlands, is associated with a severe phenotype and a high mortality. Apart from this, there is only a limited relation between the genotype and the clinical phenotype.
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PMID:Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A. 949 60

We report on a 1-year-old boy, with carbohydrate-deficient glycoprotein (CDG) syndrome type I due to phosphomannomutase deficiency. Radiologic examination of the skeleton revealed previously unreported bone abnormalities that could be included in a dysostosis multiplex: wide ribs, squared iliac wings, horizontal acetabular roofs, widening and modeling abnormalities of ischial and pubic bones, dorsolumbar kyphosis, and slight hook-like dysplasia of the first lumbar vertebrae. Wormian bones were also present. We suggest that these features may be due to hypoglycosylation of bone proteins and that CDG syndrome type I should be included in the differential diagnosis of dysostosis multiplex.
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PMID:Carbohydrate-deficient glycoprotein syndrome type I: a new cause of dysostosis multiplex. 950 11

Phosphomannose isomerase (PMI) deficiency is the cause of a new type of carbohydrate-deficient glycoprotein syndrome (CDGS). The disorder is caused by mutations in the PMI1 gene. The clinical phenotype is characterized by protein-losing enteropathy, while neurological manifestations prevailing in other types of CDGS are absent. Using standard diagnostic procedures, the disorder is indistinguishable from CDGS type Ia (phosphomannomutase deficiency). Daily oral mannose administration is a successful therapy for this new type of CDG syndrome classified as CDGS type Ib.
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PMID:Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy. 952 70

Three siblings suffered from an unusual disorder of cyclic vomiting and congenital hepatic fibrosis. Serum transferrin isoelectric focusing showed increased asialo- and disialotransferrin isoforms as seen in the carbohydrate-deficient glycoprotein (CDG) syndrome type I. Phosphomannomutase, which is deficient in most patients with type I CDG syndrome, was found to be normal in all three patients. Structural analysis of serum transferrin revealed nonglycosylated, hypoglycosylated, and normoglycosylated transferrin molecules. These findings suggested a defect in the early glycosylation pathway. Phosphomannose isomerase was found to be deficient and the defect was present in leucocytes, fibroblasts, and liver tissue. Phosphomannose isomerase deficiency appears to be a novel glycosylation disorder, which is biochemically indistinguishable from CDG syndrome type I. However, the clinical presentation is entirely different.
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PMID:A novel disorder of N-glycosylation due to phosphomannose isomerase deficiency. 953 79

From 10 patients with carbohydrate-deficient glycoprotein (CDG) syndrome due to phosphomannomutase (PMM) deficiency, out of 10 lysosomal enzymes, 7 enzyme activities were measured in serum and 9 in leukocytes. In serum there was a 2-fold to 4-fold increase in activity of beta-glucuronidase, beta-hexosaminidase, beta-galactosidase, and arylsulphatase A. In leukocytes, however, several enzymes had reduced activity, particularly alpha-fucosidase, beta-glucuronidase and alpha-mannosidase. These abnormalities could result from missorting, defective reuptake and/or reduced stability of the enzymes due to the defective glycosylation.
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PMID:Lysosomal enzyme activities in serum and leukocytes from patients with carbohydrate-deficient glycoprotein syndrome type IA (phosphomannomutase deficiency). 958 69

Two pregnancies at risk for the carbohydrate-deficient glycoprotein syndrome Type 1A (CDG1A, phosphomannomutase deficient) were monitored by enzyme and genetic linkage analyses. The index case in both families had a proven deficiency of phosphomannomutase (PMM). An unaffected fetus was predicted in family 1 following amniocentesis. Normal PMM activity was found in cultured amniotic fluid cells and there was no elevation of lysosomal enzymes in the amniotic fluid. Genetic linkage analysis using microsatellite markers closely linked to the CDG1A gene confirmed this prediction. A healthy child was born. In the second family direct assay of chorionic villi showed a profound deficiency of PMM and genetic linkage analysis showed the fetus to have the same haplotype as the proband. The pregnancy was terminated and a deficiency of PMM was confirmed in cultured fibroblasts from the fetus. Reliable prenatal diagnosis of CDG Type 1A (PMM-deficient) can be achieved by a combination of biochemical and molecular genetic tests.
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PMID:Prenatal diagnosis of the carbohydrate-deficient glycoprotein syndrome type 1A (CDG1A) by a combination of enzymology and genetic linkage analysis after amniocentesis or chorionic villus sampling. 970 50

Carbohydrate-deficient glycoprotein syndromes (CDGS) type I are a group of genetic diseases characterized by a deficiency of N-linked protein glycosylation in the endoplasmic reticulum. The majority of these CDGS patients have phosphomannomutase (PMM) deficiency (type A). This enzyme is required for the synthesis of GDP-mannose, one of the substrates in the biosynthesis of the dolichol-linked oligosaccharide Glc3Man9GlcNAc2. This oligosaccharide serves as the donor substrate in the N-linked glycosylation process. We report on the biochemical characterization of a novel CDGS type I in fibroblasts of four related patients with normal PMM activity but a strongly reduced ability to synthesize glucosylated dolichol-linked oligosaccharide leading to accumulation of dolichol-linked Man9GlcNAc2. This deficiency in the synthesis of dolichol-linked Glc3Man9GlcNAc2 oligosaccharide explains the hypoglycosylation of serum proteins in these patients, because nonglucosylated oligosaccharides are suboptimal substrates in the protein glycosylation process, catalyzed by the oligosaccharyltransferase complex. Accordingly, the efficiency of N-linked protein glycosylation was found to be reduced in fibroblasts from these patients.
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PMID:A novel carbohydrate-deficient glycoprotein syndrome characterized by a deficiency in glucosylation of the dolichol-linked oligosaccharide. 971 Apr 31


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