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)

Type I carbohydrate-deficient glycoprotein (CDG) syndrome is a genetic multisystem disorder generally without overt renal problems. We report a neonate with neurological abnormalities and congenital nephrotic syndrome of diffuse mesangial sclerosis type. Serum transferrin isoelectric focusing showed the typical abnormalities of type I CDG syndrome. Normal transferrin focusing findings in other patients with similar renal problems excluded the possibility of a secondary biochemical phenomenon. The diagnosis of type I CDG syndrome was confirmed by demonstration of a deficiency of phosphomannomutase. No evidence of pontocerebellar atrophy was found in imaging or at autopsy. We conclude that congenital nephrotic syndrome may occur in type I CDG syndrome, and that this diagnosis should be considered in patients with congenital nephrotic syndrome. Absence of pontocerebellar atrophy does not exclude the diagnosis of type I CDG syndrome.
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PMID:Congenital nephrotic syndrome: a novel phenotype of type I carbohydrate-deficient glycoprotein syndrome. 898 53

Carbohydrate-deficient glycoprotein syndrome consists of a group of disorders with multisystemic involvement and prominent neurologic symptoms. The full clinical spectrum continues to evolve, with four types currently recognized; type I is by far the most common. The clinical presentation of CDGS appears more severe in infants than in adults. Diagnosis is based on the clinical findings of characteristic fat distribution, neurologic impairment, and developmental delay, combined with the biochemical finding of cathodally migrating serum glycoproteins, transferrin in particular, on isoelectric focusing. Scientific evidence supports the hypothesis that abnormal synthesis of N-linked oligosaccharides is the basic metabolic defect in CDGS. The complex, multistep nature of the N-linked oligosaccharide pathway and the clinical heterogeneity of CDGS suggest that several different defects in the pathway can result in this disorder. Two specific enzyme defects have been reported: phosphomannomutase deficiency in some type I patients and N-acetylglucosamine transferase II deficiency in type II patients. Investigations continue into other metabolic bases of CDGS. The discovery of some of the enzyme defects paves the way for cloning, mutational analysis, and eventually prenatal diagnosis in appropriate families. No known treatment exists for CDGS; pallintive care and support is the most that can be offered. Family support systems are blossoming both in the United States and abroad, giving families the ability to communicate with each other and with workers in the field. As more cases are diagnosed and scientific research continues, advances in clinical definition, supportive care, nutrition, and prenatal diagnosis of CDGS are inevitable.
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PMID:Carbohydrate-deficient glycoprotein syndrome. 926 69

The carbohydrate-deficient glycoprotein syndrome (CDGS) is a group of disorders characterized biochemically by abnormal glycosylation of serum and cellular glycoproteins. It has been classified into four forms on the basis of the isoelectric focusing pattern of serum transferrin and difference in clinical presentation. A deficiency of phosphomannomutase (PMM) has been reported in most patients with type 1. Seven of our eight CDGS patients, classified clinically as type 1, were shown to have a deficiency of phosphomannomutase in their fibroblast or lymphoblastoid cells (0.04-0.2 nmol/min per mg, compared with a control range of 1.0-2.1 nmol/min per mg). The eighth patient, who had many clinical features of the severe neonatal form of CDGS type 1, but lacked definite signs of CNS and ocular involvement, had a normal phosphomannomutase activity in his fibroblasts. There were approximately equal amounts of disialo- and tetrasialotransferrin and only a trace amount of asialotransferrin in the serum and ascitic fluid of this patient. The disialo- and tetrasialotransferrin isoforms were purified by ion-exchange chromatography and analysed by SDS-PAGE. The disialotransferrin had a lower molecular mass than the tetrasialotransferrin, consistent with the absence of an N-linked glycan. The N-linked glycans released enzymically from both isoforms consisted exclusively of disialylated biantennary chains, suggesting that disialotransferrin results from underglycosylation, as in the PMM-deficient CDGS type 1 patients. It is concluded that the clinical and biochemical phenotype in CDGS type 1 can result from more than one basic defect.
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PMID:A case of the carbohydrate-deficient glycoprotein syndrome type 1 (CDGS type 1) with normal phosphomannomutase activity. 942 52

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

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

Deficiency of dolichyl-P-Glc:Man9GlcNAc2-PP-dolichyl glucosyltransferase is the cause of an additional type of carbohydrate-deficient glycoprotein syndrome (CDGS type V). Clinically this type resembles the classical type Ia of CDGS caused by the deficiency of phosphomannomutase. As a result of the glucosyltransferase deficiency in CDGS type V nonglucosylated lipid-linked oligosaccharides accumulate. The defect is leaky and glucosylated oligosaccharides are found on nascent glycoproteins. The limited availability of glucosylated lipid-linked oligosaccharides explains the incomplete usage of N-glycosylation sites in glycoproteins. This finding is reflected in the presence of transferrin forms in serum that lack one or both of the two N-linked oligosaccharides and the reduction of mannose incorporation to about one-third of control in glycoproteins of fibroblasts.
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PMID:Carbohydrate-deficient glycoprotein syndrome type V: deficiency of dolichyl-P-Glc:Man9GlcNAc2-PP-dolichyl glucosyltransferase. 978 65

The carbohydrate-deficient glycoprotein or CDG syndromes (OMIM 212065) are a recently delineated group of genetic, multisystem diseases with variable dysmorphic features. The known CDG syndromes are characterized by a partial deficiency of the N-linked glycans of secretory glycoproteins, lysosomal enzymes, and probably also membranous glycoproteins. Due to the deficiency of terminal N-acetylneuraminic acid or sialic acid, the glycan changes can be observed in serum transferrin or other glycoproteins using isoelectrofocusing with immunofixation as the most widely used diagnostic technique. Most patients show a serum sialotransferrin pattern characterized by increased di- and asialotransferrin bands (type I pattern). The majority of patients with type I are phosphomannomutase deficient (type IA), while in a few other patients, deficiencies of phosphomannose isomerase (type IB) or endoplasmic reticulum glucosyltransferase (type IC) have been demonstrated. This review is an update on CDG syndrome type IA.
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PMID:Carbohydrate-deficient glycoprotein syndrome type IA (phosphomannomutase-deficiency). 1057 Oct 9

Carbohydrate deficient glycoprotein syndromes (CDGS) are inherited disorders in glycosylation. Isoelectric focusing of serum transferrin is used as a biochemical indicator of CDGS; however, this technique cannot diagnose the molecular defect. Even though phosphomannomutase (PMM) deficiency accounts for the great majority of known CDGS cases (CDGS type Ia), newly discovered cases have significantly different clinical presentations than the PMM-deficient patients. These differences arise from other defects affecting the biosynthesis of N-linked oligosaccharides in the endoplasmic reticulum and in the Golgi compartment. The most notable is the loss of phosphomannose isomerase (PMI) (CDGS type Ib). It causes severe hypoglycemia, protein-losing enteropathy, vomiting, diarrhea, and congenital hepatic fibrosis. In contrast to PMM-deficiency, there is no developmental delay nor neuropathy. Most symptoms in the PMI-deficient patients can be successfully treated with dietary mannose supplements. Another defect is the lack of glucosylation of the lipid-linked oligosaccharide precursor. The clinical features of this form of CDGS are milder, but similar to, PMM-deficient patients. Yeast genetic and biochemical techniques were critical in unraveling these disorders since many of the defective genes were known in yeast and corresponding mutants were available for complementation. Yeast strains carrying mutations in the homologous genes are likely to provide conclusive identification of the primary defects in novel CDGS types that affect the synthesis and transfer of precursor oligosaccharides.
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PMID:Molecular basis of carbohydrate-deficient glycoprotein syndromes type I with normal phosphomannomutase activity. 1057 Oct 10

Physicians have become accustomed to thinking of certain inborn errors of metabolism (e.g., lysosomal, peroxisomal, and mitochondrial diseases) as being associated with specific subcellular organelles. In recent years, a family of disorders of N-glycosylation has been recognized, in which the metabolic defect is expressed in the cytosol, endoplasmic reticulum, and Golgi apparatus. These could be conveniently thought of as "prelysosomal" disorders. At least six of these entities are characterized by hypoglycosylation of many glycoconjugates, and have been designated as the carbohydrate-deficient glycoprotein syndromes. Given the ubiquity of the products of N-glycosylation in the cellular economy, it is not surprising that these defects in metabolism have protean clinical manifestations. Delayed development and other neurologic symptoms are wedded to variable dysfunctions of the heart, liver, and endocrine and coagulation systems. Patients can have dysmorphic features or cerebellar hypoplasia, attesting to the antenatal expression of these disorders. The most frequently recognized phenotype (several hundred cases worldwide) has been designated carbohydrate-deficient glycoprotein syndrome type la, and results from mutations in phosphomannomutase, a cytosolic enzyme involved in the synthesis of the lipid-linked oligosaccharide that is eventually attached to nascent glycoproteins through the amide group of asparagine residues. All forms of carbohydrate-deficient glycoprotein syndrome express an excess of hypoglycosylated isoforms of circulating transferrin, which serves as a useful screening tool. Physicians should consider screening for carbohydrate-deficient glycoprotein syndrome in individuals with delayed development, seizures, strokelike episodes, cerebellar hypoplasia, and demyelinating neuropathy with or without other signs of multisystem disease.
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PMID:Screening for "prelysosomal disorders": carbohydrate-deficient glycoprotein syndromes. 1059 62

Carbohydrate-deficient glycoprotein syndromes are rare, multisystemic diseases, typically with major nervous system impairment, that are caused by hypo- and unglycosylation of N-linked glycoproteins. Hence, a biochemical evidence of this abnormality, like hypoglycosylation of serum transferrin is essential for diagnosis. Clinically and biochemically, six types of the disease have been delineated. Three of them are caused by deficiencies of the enzymes that are required for a proper glycosylation of lipid--(dolichol) linked oligosaccharide (phosphomannomutase or phosphomannose isomerase or alpha-glycosyltransferase), and one results from a deficiency of Golgi resident N-acetylglucosaminyltransferase II. In addition one variant of the disease has been reported as due to a defective biosynthesis of dolichol iself. The diseases are heritable but genetics has been established for only two types. Therapy, based on administration of mannose to patients is currently under investigation. It benefits patients with deficiency of phosphomannose isomerase. Taking into account the complexity of N-linked glycosylation of proteins more of the disease variants is expected to be found.
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PMID:Carbohydrate-deficient glycoprotein syndromes. 1069 81


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