Carbohydrate-deficient glycoprotein syndrome: clinical expression in adults with a new metabolic disease.

Stibler, Helena; Blennow, Gösta; Kristiansson, Bengt; Lindehammer, H; Hagberg, B

doi:10.1136/jnnp.57.5.552

Cited by 85 publications

(50 citation statements)

References 18 publications

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“…11,26 -28 Patients 2 and 3 showed signs of periodic liver insufficiency as sometimes seen in other CDG patients, 1,11,29,30 and they also showed slower postnatal growth velocity based on normal values of height and weight. All the children have made developmental progress while under observation, but remain moderately delayed by comparison with their peers.…”

Section: Patient Descriptionmentioning

confidence: 90%

Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia

Westphal

Peterson

Patterson

et al. 2001

Genetics in Medicine

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Purpose: Congenital disorders of glycosylation (CDG) result from mutations in N-glycan biosynthesis. Mutations in phosphomannomutase (PMM2) cause CDG-Ia. Here, we report four clinically mild patients and their mutations in PMM2. Methods: Analysis of the PMM2 cDNA and gene revealed the mutations affecting the glycosylation efficiency. Results: The patients have 30% to 50% normal PMM activity in fibroblasts due to different mutations in PMM2, and we studied the effect of each mutation on the PMM activity in a Saccharomyces cerevisiae expression system. Conclusions: Each patient carried a severe mutation that decreased the PMM activity to less than 10% as well as a relatively mild mutation. A new mutation, deletion of base 24, changed the reading frame. The C9Y, C241S, and L32R mutations showed 27% to 45% activity when expressed in the eukaryotic expression system, and the more severe D148N was shown to be thermolabile. Genet Med 2001:3(6):393-398.

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Section: Patient Descriptionmentioning

confidence: 90%

Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia

Westphal

Peterson

Patterson

et al. 2001

Genetics in Medicine

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“…Two sisters were diagnosed with CDGS on the basis of their clinical presentation including low birth weight, poor feeding, hypotonia, ataxia, strabismus, hepatomegaly, seizures, autistic-like behavior, characteristic fat pads, and a cathodal shift of serum transferrin in isoelectric focusing. Based upon the severity and extent of the symptoms, these patients fall into the Type I classification of Jaeken (9,14).…”

Section: Methodsmentioning

confidence: 99%

“…Within the first few months of life, affected children present with neurological abnormalities, and their development is marked by variable but often severe psychomotor retardation, lower motor neuron dysfunction, abnormal facies, skeletal anomalies, variable hepatomegaly, and other clinical symptoms and signs. Since its initial description, the syndrome has been reported in populations from around the world, and the existence of distinct subtypes based on the severity of clinical symptoms has been suggested (10)(11)(12)(13)(14). A characteristic biochemical abnormality of this syndrome was discovered serendipitously in the isoelectric focusing of serum transferrin (1)(2)(3)15), a test originally devised to screen for alcohol abuse in normal adults (16).…”

Section: Introductionmentioning

confidence: 99%

Carbohydrate-deficient glycoprotein syndrome: not an N-linked oligosaccharide processing defect, but an abnormality in lipid-linked oligosaccharide biosynthesis?

Powell¹,

Paneerselvam²,

Vij³

et al. 1994

J. Clin. Invest.

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The carbohydrate-deficient glycoprotein syndrome (CDGS) is a developmental disease associated with an abnormally high isoelectric point of serum transferrin. Carbohydrate analyses of this glycoprotein initially suggested a defect in N-linked oligosaccharide processing, although more recent studies indicate a defect in the attachment of these sugar chains to the protein. We studied both serum glycoproteins and fibroblast-derived [2-3H]mannose-labeled oligosaccharides from CDGS patients and normal controls. While there was a decrease in the glycosylation of serum glycoproteins of affected individuals, differences were not seen in either monosaccharide composition or oligosaccharide structures. The lectin-binding profiles of glycopeptides from [2-3H]-mannose-labeled fibroblasts were likewise indistinguishable. However, the incorporation of [2-3H]mannose into both glycoproteins and the dolichol-linked oligosaccharide precursor was significantly reduced. Thus, at least in some patients, CDGS is not due to a defect in processing of N-linked oligosaccharides, but rather to defective synthesis and transfer of nascent dolichol-linked oligosaccharide precursors. This abnormality could result in both a failure to glycosylate some sites on some proteins, as well as secondary abnormalities in overall glycoprotein processing and/or function. (J.

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“…Sie werden unter dem Begriff CDG (congenital disorders of glycosylation, ehemals carbohydrate-deficient-glycoprotein-syndrome) zusammengefasst [16,20,26]. Berichte über Patienten jenseits des Kindesalters sind bislang eine Rarität [38].…”

Section: Zusammenfassungunclassified

CDG (congenital disorders of glycosylation) Zur Differenzialdiagnose hereditärer Ataxien im Erwachsenenalter

et al. 2002

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Congenital disorders of glycosylation (CDG) are a group of hereditary multisystem diseases due to different defects of enzymes or transport molecules involved in the synthesis of glycoproteins. CDG-la is the most common subtype, with cerebellar ataxia as the main neurological symptom. Currently there is little information about CDG-la manifestation in adulthood. Here we present two sisters in whom the diagnosis of CDG-la was made in the fourth decade of life and who to our knowledge are the oldest known patients with the disorder in Germany. The clinical course of the disease was typical, although less severe than previously described. The carbohydrate-deficient transferrin (CDT) level was increased but lower than in other CDG patients. Isoelectric focusing of transferrin revealed changes typical of CDG, whereas those of alpha 1-antitrypsin were only moderately pathologic. This might be due to the milder manifestation of the disease in our patients or it could be indicative of a stabilization of the disease after puberty. The CDG should be included in the differential diagnostic workup of hereditary cerebellar ataxia in adults.

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Carbohydrate-deficient glycoprotein syndrome: clinical expression in adults with a new metabolic disease.

Abstract: A new group of recessively inherited metabolic disorders affecting glycoprotein metabolism has been identified-the carbohydrate-deficient-glycoprotein

Cited by 85 publications

References 18 publications

Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia

Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia

Carbohydrate-deficient glycoprotein syndrome: not an N-linked oligosaccharide processing defect, but an abnormality in lipid-linked oligosaccharide biosynthesis?

CDG (congenital disorders of glycosylation) Zur Differenzialdiagnose hereditärer Ataxien im Erwachsenenalter

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