Summary congenital disorders of glycosylation cdg is an umbrella term for a rapidly. Cdg carbohydrate deficient transferrin for congenital disorders of glycosylation, serum. Glycosylation is the process by which sugar trees glycans are created, altered and chemically attached to. Carbohydrate deficient transferrin cdt is a laboratory test used to help detect heavy ethanol consumption physiology. The clinical characteristics are variable, but often include psychomotor, growth, and mental. Phosphomannomutase deficiency is a cause of carbohydratedeficient glycoprotein syndrome type i. Carbohydratedeficient glycoprotein syndromes ncbi nih. Congenital disorder of glycosylation type 1c conditions. Anesthetic management of a boy with congenital disorder of. Up to this date, six different gene defects have been elucidated. This website is maintained by the national library of medicine. The first described andbest known, type i, seems to affect earlyneuronal development,whereas.
Inhibition of phosphomannose isomerase by fructose 1. It is the second largest subtype of cdg summary by sun et al. Lack of hardyweinberg equilibrium for the most prevalent. Sep 21, 2011 genetics home reference ghr contains information on pmm2cdg cdg ia. Congenital disorders of glycosylation cdg, formerly known as carbohydrate deficient glycoprotein syndrome, are a group of over 100 inherited metabolic disorders affecting several steps of the pathway involved in the glycosylation of proteins. Recently, researchers have proposed a classification system that names each subtype by the official abbreviation of its defective gene followed by a dash and cdg. Serum total nlinked glycans, transferrin, and apolipoprotein ciii. Here we describe conserved genotypephenotype relationships across yeast and human patients between five pmm2 lossof. Cdg care genetic and rare diseases information center. Mutations in human andor mouse homologs are associated with this disease. Phosphomannomutase deficiency is a cause of carbohydrate deficiency glycoprotein syndrome type i.
Due credit and reputation for authors authorship tracking technology. Carbohydrate deficient transferrin cdt is one of the mostly employed biomarkers to assess chronic alcohol abuse in clinical and forensic medicine bortolotti et al. Relevant clinical information and the indications for the analysis should be provided with the specimen, in particular in nonpediatric patients. Congenital disorders of glycosylation cdg are usually diagnosed by isoelectric focusing ief of serum transferrin tf. Cdg were first reported in the medical literature in 1980 by dr. The carbohydratedeficient glycoprotein or cdg syndromes omim 212065 are a recently delineated group of genetic, multisystem diseases with variable dysmorphic features. Several different names have been used to describe these disorders including carbohydratedeficient glycoprotein syndromes. Yeast models of phosphomannomutase 2 deficiency, a congenital. Cdg abbreviation stands for carbohydrate deficient glycoprotein. Genetics home reference ghr contains information on pmm2. The plethora of defects that will eventually be identified makes it indispensable to use a simple and straightforward nomenclature for this group of diseases. Pmm2cdg nord national organization for rare disorders. The first, carbohydrate deficient glycoprotein cdg syndrome i, is now fairly well delineated by clini cal and biologic patterns 1,2. 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.
Transferrin comprises a single polypeptide chain with two polysaccharide chains ended by a sialic acid residue. Congenital disorders of glycosylation cdg result from mutations in. The type and severity of problems associated with pmm2cdg vary widely among affected individuals, sometimes even among members of the same family. Transferrin mutations at the glycosylation site complicate.
Carbohydratedeficient glycoprotein syndrome by hirsch. In its most abundant form, this serum glycoprotein carries two complex n. The prenatal diagnosis of cdg syndrome can be achieved, once the diagnosis is confirmed in the index case. Carbohydratedeficient glycoprotein clinical expression in. Congenital disorder of glycosylation type ia myriad womens health. More than 100 different forms of cdg have been reported in the ensuing years.
Congenital disorders of glycosylation cdg, formerly known as carbohydrate deficient glycoprotein syndrome, are a group of over 100 inherited metabolic disorders affecting several steps of the pathway involved in the glycosylation of. Pmm2congenital disorder of glycosylation pmm2cdg, also known as congenital disorder of glycosylation type ia is an inherited condition that affects many parts of the body. Gonadal function and glycoprotein hormones in the carbohydrate deficient glycoprotein cdg syndrome. Pmm2 orthologs are present in model organisms, including the budding yeast saccharomyces cerevisiae gene sec531. If either pmm2cdg cdgia or mpicdg cdgib is suspected, order pmmil phosphomannomutase and phosphomannose isomerase, leukocytes. The cerebellum was hypoplastic at presentation in 4 cases, progressive. The metabolism of the carbohydrates galactose, fructose, and glucose is intricately linked through interactions between different enzymatic pathways, and disorders that affect these pathways may have symptoms ranging from mild to severe or even lifethreatening. During the last few years, progress in identifying the molecular defects of the carbohydrate deficient glycoprotein syndromes has been very rapid. Carbohydrate deficient transferrin for congenital disorders of glycosylation, serum test is useful for the diagnosis of the various forms of congenital disorders of glycosylation cdg. Congenital disorders of glycosylation cdg represent a constellation of diseases that result from defects in the synthesis of carbohydrate structures glycans and in the attachment of glycans to other compounds. Man1b1cdg genetic and rare diseases information center. Congenital disorders of glycosylation cdg, formerly named carbohydrate deficient glycoprotein syndrome, are rare hereditary disorders caused by mutations in the genes coding for enzymes involved in the biosynthesis of glycoproteins and other glycoconjugates. Summary congenital disorders of glycosylation cdg is an umbrella term for a rapidly expanding group of rare genetic, metabolic disorders due to defects in complex chemical process known as glycosylation.
Congenital disorders of glycosylation cdg, formerly named carbohydratedeficient glycoprotein syndrome, are rare hereditary disorders caused by mutations in the genes coding for enzymes involved in the biosynthesis of glycoproteins and other glycoconjugates 1. The known cdg syndromes are characterized by a partial deficiency of the nlinked glycans of secretory glycoproteins, lysosomal enzymes, and probably also membranous glycoproteins. How is carbohydrate deficient glycoprotein syndrome type i abbreviated. Carbohydrate deficient transferrin as a marker of chronic alcohol abuse.
Cdgs types ia and ib have been related to deficiencies of phosphomannomutase and phosphomannose isomerase, respectively, while cdgs type ii results from a deficiency. Four types of carbohydratedeficient glycoprotein syndrome have been described, and the cause of two of them has been found. Carbohydratedeficient transferrin cdt as a biochemical tool for the screening of congenital disorders of glycosylation cdgs article in clinical biochemistry 4018. Keywords carbohydrate deficient glycoprotein, glycosylations disorder, phosphomannomutase deficiency name of the disease and synonyms cdg syndrome congenital disorders of glycosylation previously carbohydrate deficient glycosylation syndrome. Carbohydrate deficient glycoprotein syndrome type iij. Carbohydratedeficient transferrin cdt, defined by 2 sialo and 0 sialo isoforms, is a marker of chronic alcohol abuse. Cdg i carbohydratedeficient glycoprotein syndrome type i. Cdg 1a is an earlyonset neurodegenerative disease with selective hindbrain involvement and highly variable clinical presentation.
Cdgs, formerly known as carbohydrate deficient gly. The symptoms and signs of these syndromes are described, with variations that occur at different ages. There are several isoforms of human transferrin with different levels of sialylation. Carbohydratedeficient glycoprotein syndrome type ia. Lack of homozygotes for the most frequent disease allele. The r141h mutation in the pmm2 gene is the most frequent mutation in type ia of the congenital disorders of glycosylation formerly carbohydrate deficient glycoprotein syndromescdgia. Transferrin is an 80kda serum glycoprotein produced by the liver. The basic defects are probably in the glycosylation pathway endoplasmic reticulum, golgi apparatus or postgolgi. We performed 792 cze analyses of tf, using the ceofixtmcdt carbohydrate deficient transferrin assay. If the ordering physician is looking for evaluation of alcohol abuse, order cdta carbohydrate deficient transferrin, adult, serum. Diagnostic tools in congenital disorders of glycosylation.
Cdg carbohydrate deficient transferrin for congenital disorders of glycosylation, serum nglycan, oglycan, and cog complex defects serum total nlinked glycans, transferrin, and apolipoprotein ciii. Cdg ic is characterized by psychomotor retardation with delayed walking and speech, hypotonia, seizures, and sometimes proteinlosing enteropathy. Cdg i stands for carbohydrate deficient glycoprotein syndrome type i. Carbohydrate deficient transferrin for congenital disorders. The three types notwithstanding, clinical presentation and. The use of propofol based anesthesia, as well as the use of longer acting muscle relaxants and opioides may result in prolonged eduction and undesirable adverse reactions. In cdg syndrome type i, as a consequence of an early glycosylation defect, there is a partial deficiency of the glycoprotein sugar moieties. Cdg type ia and congenital cytomegalovirus infection. The carbohydrate deficient glycoprotein cdg syndromes are a newly recognized family of diseases with autosomal recessive inheritance. Cdg carbohydratedeficient glycoprotein acronymfinder. Jaeken syndrome phosphomannomutase 2 deficiency carbohydratedeficient glycoprotein syndrome, type ia. Phosphomannomutase 2 deficiency pmm2 cdg is the most common monogenic congenital disorder of glycosylation cdg affecting at least 800 patients globally.
The commonest is type ia with an autosomal recessive form of inheritance, and the gene responsible has been mapped to 16p. Cdgn congenital disorders of nglycosylation, serum. The identification of abnormal glycoforms of serum transferrin in carbohydrate deficient glycoprotein syndrome type i by capillary zone electrophoresis. The national organization for rare disorders nord has a report for patients and families about this condition. The aim of this study was to evaluate capillary zone electrophoresis cze as a diagnostic alternative to ief. Iourin o, mattu ts, mian n, keir g, winchester b, dwek ra, et al. Carbohydrate deficient glycoprotein syndrome cdgs type ia, congenital disorder of glycosylation cdg type ia,phosphomannomutase deficiency,jaeken syndrome, pmm2cdg, cdg1a.
Carbohydrate deficient glycoprotein syndrome type 1 cdg1. Pmm2 cdg cdg ia previously known as congenital disorder of glycosylation type 1a, the most common of a group of disorders of abnormal glycosylation of nlinked oligosaccharides, is divided into three types. For a discussion of the classification of cdgs, see cdg1a 212065. Carbohydratedeficient glycoprotein syndrome type i. Diagnostic screening of cdg is performed by isoelectric focusing ief of transferrin. Congenital disorders of glycosylation are a heterogeneous group of disorders with multisystemic involvement. Congenital disorders of glycosylation are sometimes known as cdg syndromes. The cdg syndrome orphanet encyclopedia, september 2004. The carbohydrate deficient glycoprotein syndromes are a group of congenital multisystemic diseases characterized by defective glycosylation of nglycans. Several different names have been used to describe these disorders including carbohydrate deficient glycoprotein syndromes. What is the abbreviation for carbohydrate deficient glycoprotein. The worlds first wiki where authorship really matters. Screening for congenital disorders of glycosylation.
Cdg carbohydrate deficient glycoprotein syndrome cdgs specimen collection requirements. Diagnosis of congenital disorders of glycosylation by. Congenital disorders of glycosylation cdgs are a rapidly growing group of inherited disorders caused by defects in the synthesis and processing of the asparagineasnlinked oligosaccharides of. Four types of carbohydrate deficient glycoprotein syndrome have been described, and the cause of two of them has been found. Protein glycosylation is an essential posttranslational modification of various proteins, affecting their folding, sorting, and function. Nearly 100 european pa tients have been identified at the 2 main diagnostic cen. Cdg abbreviation stands for carbohydratedeficient glycoprotein. Cdg i carbohydratedeficient glycoprotein syndrome type. Carbohydratedeficient glycoprotein syndrome how is. Type i cdg is characterized by defects in the assembly or transfer of the dolichol. The congenital disorders of glycosylation type i cdg i are autosomal recessive disorders characterized by a defective assembly of the nglycans of the complex glycoconjugates.
Most patients show a deficiency of phosphomannomutase pmm, the enzyme that converts mannose 6phosphate to mannose 1phosphate in the synthesis of gdpmannose. The carbohydrate deficient glycoprotein cdg syndromes cdgs are a series of autosomal recessive enzyme deficiencies which result in incomplete glycosylation of plasma proteins. Carbohydrate deficient transferrin for congenital disorders of glycosylation, serum. Cdt is defined as the ratio between disialotf and total tf, the latter measured as the sum of all sialoforms bortolotti et al. Carbohydratedeficient glycoprotein syndrome cdgs type ia.
Dueto unique carbohydrate defects in secretoryglycoproteins theyhavebeentermed carbohydrate deficient glycoprotein cdg syndromes, of which three clinical and biochemical types havenowbeenidentified. Some cdg types can be detected by a blood test for missing sugar building blocks called a carbohydrate deficient transferrin, cdt, or transferrin ief, but sometimes this blood test can be normal in cdg. What is the abbreviation for carbohydratedeficient glycoprotein. Genetic testing is the most reliable test for determining cdg. Carbohydrate deficient glycoprotein cdg syndrome type i article pdf available in journal of medical genetics 341. The most common form is phosphomannomutase deficiency or congenital disorders of glycosylation type ia with an autosomal recessive inheritance and incidence estimated at 120000 150000 live born. The discovery of this disease was based on the observation by jaeken et al. Pmm2 deficiency or pmm2cdg is a very rare genetic disorder caused by mutations in pmm2. Imagine a global collaborative knowledge base for original thoughts nature genetics. Metabolic disease disorders of carbohydrate metabolism. Skeletal dysplasia and myelopathy in congenital disorder. Cdg i is defined as carbohydrate deficient glycoprotein syndrome type i somewhat frequently. Functional significance of pmm2 mutations in mildly.
Test code cdg carbohydrate deficient transferrin for. The congenital disorders of glycosylation or carbohydratedeficient glycoprotein cdg syndrome is a group of autosomal recessive diseases that affect the. Wikigenes carbohydratedeficient glycoprotein syndrome. Pmm2cdg cdgia genetic and rare diseases information. Lack of homozygotes for the most frequent disease allele in. Carbohydratedeficient glycoprotein syndromes become.
Pmm2 deficiency or pmm2cdg is a very rare genetic disorder caused by mutations. The known cdg syndromes are characterized by a partial deficiency of the n linked glycans of secretory glycoproteins, lysosomal enzymes, and probably also membranous. The disease is linked to chromosome 16p, and mutations. Carbohydratedeficient glycoprotein syndrome type ii. Endocrinology of the carbohydrate deficient glycoprotein syndrome type 1 from birth through adolescence. Pdf carbohydrate deficient glycoprotein cdg syndrome. The most common form is phosphomannomutase deficiency or congenital disorders of glycosy. Carbohydrate deficient glycoprotein cdg syndrome type i. Carbohydratedeficient glycoprotein how is carbohydrate. In the present state of our knowledge the central nervous system is always severely affected but nearly all other organs are involved to a. Carbohydratedeficient glycoprotein syndrome, type 1a. Carbohydratedeficientglycoprotein syndrome type 1 cdg1.
Four types of carbohydratedeficient glycoprotein syndrome have been described. Carbohydrate deficient glycoprotein syndrome listed as cdgs. Clinical and molecular features of three patients with. Carbohydratedeficient glycoprotein syndromes postgraduate. Cdg carbohydrate deficient transferrin for congenital disorders of glycosylation cdgs carbohydrate deficient transferrin for congenital disorders of glycosylation cdt carbohydrate deficient transferrin for congenital disorders of. Collect serum one 4 ml plain red or gold serum separator tube. Transferrin is a serum protein that carries iron through the bloodstream to the bone marrow, where red blood cells are manufactured, as well as to the liver and spleen. Carbohydratedeficient transferrin cdt as a biochemical. It is carbohydrate deficient glycoprotein syndrome. This test is for congenital disorders of glycosylation. Congenital disorders of glycosylation cdg, formerly known as carbohydratedeficient glycoprotein syndrome, are a group of over 100 inherited metabolic disorders affecting several steps of the pathway involved in the glycosylation of proteins.
General discussion summary congenital disorders of glycosylation cdg is an umbrella term for a rapidly expanding group of rare genetic, metabolic disorders due to defects in complex chemical process known as glycosylation. Nord is a patient advocacy organization for individuals with rare diseases and the organizations. Cdg 1k, cdg1k, alg1cdg cdgik, congenital disorder of glycosylation, type ik, cdg syndrome type ik, cdgik, carbohydrate deficient glycoprotein syndrome type ik, congenital disorder of glycosylation type 1k, mannosyltransferase 1 deficiency, alg1cdg, congenital disorder of glycosylation type ik. In cdg syndrome type i, as a consequence of an early glycosylation defect, there is a partial deficiency of the glycoprotein sugar moieties including the terminal sialic acid. A carbohydrate deficient glycoprotein syndrome cdgs is relatively rare but probably significantly underdiagnosed. The carbohydratedeficient glycoprotein cdg syndromes are a newly recognized family of diseases with autosomal recessive inheritance. Congenital disorders of glycosylation nord national. Pmm2cdg cdgia previously known as congenital disorder of glycosylation type 1a, the most common of a group of disorders of abnormal glycosylation of nlinked oligosaccharides, is divided into three types. Carbohydrate deficient glycoprotein syndrome type ii due to man1b1 deficiency. Carbohydrate deficient glycoprotein syndrome carbohydrate deficient transferrin for congenital diso. A congenital disorder of glycosylation previously called carbohydrate deficient glycoprotein syndrome is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins andor lipids is deficient or defective. Testing for congenital disorders of glycosylation by hplc. The carbohydratedeficient glycoprotein cdg syndromes cdgs are a series of autosomal recessive enzyme deficiencies which result in incomplete glycosylation of plasma proteins. Carbohydratedeficient glycoprotein cdg syndromes are a series of genetic.
Metabolic disease metabolic disease disorders of carbohydrate metabolism. Carbohydrate deficient glycoprotein syndrome symptoms, causes, diagnosis, and treatment information for carbohydrate deficient glycoprotein syndrome congenital disorder of glycosylation type 1a with alternative diagnoses, fulltext book chapters, misdiagnosis, research treatments, prevention, and prognosis. A congenital disorder of glycosylation previously called carbohydrate deficient glycoprotein syndrome is one of several rarein born errors of metabolism in which glycosylation of a variety of tissue proteins andor lipids is deficient or defective. It is an inherited metabolic disorder that was only discovered in 1989. Carbohydratedeficient glycoprotein syndrome, type ia. Home carbohydrate deficient transferrin for congenital disorders of glycosylation, serum. Its function is to carry iron around an organism mediated by ironbinding properties. Carbohydrate deficient glycoprotein syndrome type iif.
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