Congenital disorders of glycosylation: narration of a story through its patents

Congenital disorders of glycosylation are a group of more than 160 rare genetic defects in protein and lipid glycosylation. Since the first clinical report in 1980 of PMM2-CDG, the most common CDG worldwide, research made great strides, but nearly all of them are still missing a cure. CDG diagnosis has been at a rapid pace since the introduction of whole-exome/whole-genome sequencing as a diagnostic tool. Here, we retrace the history of CDG by analyzing all the patents associated with the topic. To this end, we explored the Espacenet database, extracted a list of patents, and then divided them into three major groups: (1) Drugs/therapeutic approaches for CDG, (2) Drug delivery tools for CDG, (3) Diagnostic tools for CDG. Despite the enormous scientific progress experienced in the last 30 years, diagnostic tools, drugs, and biomarkers are still urgently needed. Supplementary Information The online version contains supplementary material available at 10.1186/s13023-023-02852-w.

the same condition, the limited knowledge and unclear underlying biology of many rare diseases, the lack of sufficient medical expertise as well as the lack of rare disease awareness and adequate financial resources, still pose significant challenges to patients, clinicians, and scientists [7][8][9].
Congenital disorders of glycosylation (CDG) are a varied group of rare genetic diseases characterized by protein and lipid hypoglycosylation [10,11].In 1980, prof.Jaak Jaeken described a new neurological disorder in twin girls [12].This disorder's clinical features, stages, progression, and biochemical analyses were depicted in 1991 [13].The genetic evidence that phosphomannomutase 2 deficiency was the basis for the disease defined as "carbohydrate-deficient glycoprotein syndrome" was obtained in 1997 [14].The scientific CDG community has come a long way since then, with an ever-growing number of new patients, new CDG, clinicians and researchers committed to this field, and a large body of research papers related to clinical, genetic, biological and biochemical

Background
According to the Orphan Drug Act, a rare disease is a disease or condition that impacts fewer than 200,000 people in the US [1,2].European Union considers as rare a disease affecting fewer than 5 people in 10,000 [3].Over 6,000 rare diseases have been identified, affecting 8-10% of the world's population [4][5][6].
The low prevalence of each disease, the wide diversity of symptoms and signs that vary not only from disease to disease but also from patient to patient suffering from Orphanet Journal of Rare Diseases results, diagnosis, and treatments.However, most CDG still do not have a cure, and a correct diagnosis is often challenging to obtain in a reasonable time [7].This mini-review looks at CDG through Intellectual Property (IP) indicators.Many reviews on CDG have been published (about 40 only from 2021 to today -Pubmed access on 24th April 2023).Most focus on clinical signs and management, others on pathophysiology or treatment options.Here, we narrate the story of CDG through the associated patents.

Research outcomes
For this review, we used a combination of keywords related to CDG to search the Espacenet database [15].Queries are specified in Table 1, and the original files are available as Supplementary Files 1, 2, 3 and 4.
We manually analyzed the extracted lists.First, we merged the lists based on the title.Then, patents were selected based on the title and the bibliographic data.We only considered English-written patents that included the original documents.In the cases where the original document was not in English, but the patent had another publication number whose original document was in English, we used the last one.We also considered patents written in other languages whose original document contained an abstract written in English.Refinement of the results included eliminating duplicates and defining a final subset containing 43 patents (Supplementary File 5).
A final reading of the complete original documents allowed a classification in the following classes: (1) Drugs/therapeutic approaches for CDG, (2) Drug delivery tools for CDG, (3) Diagnostic tools for CDG, (4) Production/modification/characterization of glycoconjugates.We discharged the last group, which is not strictly specific to CDG.
Figure 1 shows the distribution of the final list of 43 patents − 25 in class 1 (Drugs/Therapeutic Approaches), 2 in class 2 (Drug Delivery Tools), and 17 in class 3 (Diagnostic Tools) -that were further analyzed and commented on.One patent (EP2905621A1) overlaps both classes 1 and 3.
On the other hand, as expected, the patents regarding drugs and drug delivery tools were produced mainly in the last decade due to the increasing knowledge of the basic molecular mechanisms of the diseases, the development of cell models, the identification of biomarkers, and the development or improvement of biotechnologies such as genetic manipulation.
Figure 3 shows the distribution of patents according to the applicant's country.Most applicants were from the US (31; 60%).According to the data provided by the World Intellectual Property Organization (WIPO), "More than 85% of all patent filings in 2021 occurred in the IP offices of China, the US, Japan, the Republic of Korea and the EPO (European Patent Office).China accounted for 46.6% of the world total." However, according to this site, applicants from China filed firstly in 'Computer technology' , secondarily in 'Digital communication' , and thirdly in 'Electrical machinery, apparatus, energy'; US applicants filed mostly in 'Computer technology' too, but their second top technology for applications is 'Medical technology' [30].Even if our results represent

Drugs/therapeutic approaches and drug delivery tools for CDG
Table 2 lists patents on drugs and therapeutic approaches, while Table 3 lists those related to drug delivery tools.

Protein N-glycosylation (PMM2-CDG, MPI-CDG, ALG11-CDG)
Nutritional intervention with oral supplementation of sugars or their derivatives has been largely practised among CDG and is still today [31].
Oral mannose supplementation therapy was the first therapeutic approach for the PMM2-CDG, as it successfully restored glycosylation in patients' fibroblasts [32].However, no clinical improvement was recorded in PMM2-CDG children during the treatment, so this was dismissed for PMM2-CDG [33].This treatment did not cause adverse effects on patients [34]; thus, in 1998,      upon promising results obtained in vitro using MPI-CDG patient fibroblasts, mannose was orally administered to a newly identified MPI-CDG patient.His clinical symptoms disappeared, and his transferrin glycoprofile normalized (DE19758059A1, [35]).This therapeutic approach has proven to be an effective therapy for MPI-CDG patients [36,37], and it has been approved both in the EU and the US.International consensus guidelines regarding managing MPI-CDG and oral administration of mannose have been recently proposed [38].However, liver transplantation might be needed since limited results have been recorded as to the liver disease [39,40].
PMM2-CDG is the most frequent CDG, with more than 1000 patients diagnosed worldwide.Seven out of 25 patents regarding CDG drugs or therapeutic approaches are related to this condition.It is a disorder of N-linked protein glycosylation, due to defective assembly and transfer of oligosaccharides to protein asparagine residues.
Biochemical characterization of wild-type and mutant PMM2 [41][42][43][44][45], and the knowledge of the molecular mechanisms underlying the disease, allowed the identification of (pro)drugs and the exploration of different therapeutic approaches, which have been an object of patents, too [14,46,47].The first two patents pursued the substrate replacement therapy approach (SRT).The enzyme variants decrease GDP-mannose levels due to a reduced conversion of mannose-6P into mannose-1P.GDP-mannose plays an essential role in N-glycan biosynthesis.The approach explored by patents WO03104247A2 and US2009054353A1 featured the supplementation of mannose-1P.However, this monophosphate is highly polar and cannot diffuse through the cell membrane.On the other hand, hydrolytic enzymes (in the stomach, intestine, and plasma) cause the degradation of monosaccharide monophosphates, limiting their absorption and bioavailability.Thus, the attention moved to the production of derivatives of mannose-1P with increased lipophilicity, namely hydrophobically masked mannose-1P (the WO03104247A2, [48]) and mono-(mannopyranosyl-1), di(mannopyranosyl-1) and tri(mannopyranosyl-1) phosphates (the US2009054353A1, [49]).Endogenous nonspecific enzymes (such as esterases or hydrolases) would ensure the release of the free monophosphate sugar.Ultimately, this approach would permit bypassing the deficient PMM2 activity.
A second exciting approach is using MPI inhibitors to treat PMM2-CDG (WO2011116355A2).PMM2 and MPI compete for mannose-6P.The efficacy of the inhibition of MPI would push the flux of mannose-6P towards the production of mannose-1P [50].The application of the MPI inhibitor successfully led to the diversion of mannose-6P towards PMM2 and improved the defective N-glycosylation, at least in pre-clinical studies.
A galactose supplementation therapy has also been explored for PMM2-CDG, and an open-label pilot trial has been conducted, but the suitability of this approach has not been fully addressed (EP3806866A1, NCT02955264, [51]).
Despite promising results in vitro, substrate replacement therapy and MPI inhibition have not been approved for PMM2-CDG.However, carbohydrate replacement therapy could become feasible thanks to the refinement of the drug delivery systems that were the object of two patents listed in Table 3. Specifically, both the selected patents regarding the tools for drug delivery (EP3954360A2 and US2022184107A1) describe the preparation of liposomes designed to deliver mannose-1-phosphate.A phase 2 clinical trial of GLM101 for treating PMM2-CDG is underway (NCT05549219).
Recently, another therapeutic approach has been attempted in diseases caused by missense variants where a mutation causes a destabilization, i.e., the use of pharmacological chaperones (PCs) [52].In these cases, an accurate evaluation of the effect of missense variants on the protein functioning or stability is needed, as it would be difficult to distinguish between disease and non-disease variants [ [53][54][55] clearly.
In CDG research, this PC therapy is still in its early steps of in vitro investigation.For PMM2-CDG, extensive screening of commercial molecules and rational drug design led to the identification of putative PCs (EP3275863A1, [56,57]).
The most recent patents regarding drugs to treat PMM2-CDG patients relate to the application of aldose reductase inhibitors (patents WO2020040831A1 [58], US2022017535A1, and WO2021071965A1).
A high-throughput screening of commercially available drugs led to identifying and rationalising this class of compounds for therapeutic purposes.The use of patientderived fibroblasts, as well as worm and yeast models, ensured the success of this study.Among the AOR inhibitors, epalrestat gained much attention.It is commonly used for treating diabetic neuropathy in Japan and is the only antidiabetic aldose reductase inhibitor approved for use in humans.A phase 3 clinical trial is currently in progress (NCT04925960).The rationale for its efficacy is that it may shunt glucose from the polyol pathway to glucose-1,6-bisphosphate, which is an endogenous stabilizer and coactivator of PMM2 homo-or hetero-dimerization [27,57,59,60].
Dietary supplementation and organ transplantation currently represent the only curative therapies available for CDG; most patients can only receive symptomatic and preventive treatments.In this frame, the therapeutic application of cannabidiol (CBD) could represent another available tool.In 2018, the FDA approved CBD for treating seizures associated with rare epilepsy syndromes [61,62].As an expansion of this application, CBD significantly reduced the number of seizures in an ALG11-CDG patient (GB2597315A).

Disorders of multiple glycosylation pathways (PGM1-CDG and GNE-CDG)
Nucleotide sugars are the building blocks of glycans; several therapeutic approaches rely on treatments that aim to increase the intracellular concentration of these molecules.This approach produced some patents, mainly regarding disorders of multiple glycosylation pathways such as PGM1-CDG, PGM3-CDG and GNE-CDG.
An example of this approach is the combined therapy of uridine prodrug and sugars (WO2016028894A1), an approach tested in three patients with a different CDG (GNE-myopathy, PGM1-CDG, and DPAGT1-CDG); the coadministration of uridine triacetate and the specific sugar caused increased intracellular concentrations of the UDP-sugar.In a second approach, a sugar supplementation therapy combined UDP-glycans and D-galactose (PMM2-CDG and MPI-CDG) (EP3806866A1).This approach looks like an evolution of the dietary intervention through monosaccharide supplementation, primarily explored in CDG, although not all trials have succeeded [63].Galactose therapy trials significantly improved biochemical abnormalities, but no clinical progression data have been reported.A metabolomic study shed light on the mechanism of PGM1-CDG and suggested that: "The direct administration of nucleotide sugars may be a more effective and less onerous form of treatment for affected individuals than galactose therapy." Such an approach could represent a starting point for other CDG related to nucleotide sugar metabolism and transport [64].
Substrate replacement therapies have also been patented for GNE-CDG.Variations in GNE cause a decrease in activity in either the isomerase or kinase protein domains, resulting in less formation of ManNAc-6-P and, ultimately, less Neu5AcA (sialic acid).In one study, N-acetyl mannosamine and derivatives proved helpful in treating myopathies, muscular atrophy or muscular dystrophy and kidney conditions and diseases in mice (EP3175859A1, [65]).On the other hand, in a phase 1 study, sialic acid was administered to patients (WO2013109906A2, [66]).In a third approach, a prodrug -a phosphoramidate derivative of ManNAc 6-phosphate -has been preferred to the monosaccharide monophosphate (WO2019118486A1, [67]).
Gene therapy is also starting to be applied in CDG, as described for PGM1-CDG (WO2022272056A2, [68]).

O-glycosylation (α-dystroglycanopathies)
Dystroglycanopathies are a subset of muscular dystrophies due to reduced O-glycosylation in α-dystroglycan with diminished laminin-binding activity.Specific molecules can enhance this binding, as it happens for a bispecific antibody.It comprises a first binding domain that binds an extracellular portion of α-dystroglycan and a second binding domain that binds laminin-2 [69].This approach is the object of patent US10221168B1.The unexpected discovery that ribitol can restore or enhance functional glycosylation of mainly α-dystroglycan led to the application of a sugar supplementation therapy that had also been a subject of a patent (US10456367B2, [70]).Also, small molecules enhancing functional O-mannosylation of α-dystroglycan have been identified (US10221168B1, [71]).These compounds proved active in several applications; they could improve the functional O-mannosylation of α-dystroglycan on B421 cells (partially deficient in DPM2 with a point variant) and FKRP defective cells.DPM2-CDG is a disorder of multiple glycosylation pathways, while FKRP-CDG is a disorder of O-mannosylation.
Gene replacement therapy for FKRP-CDG received great attention.Four patents have been produced (US2017368199A1, [72]; WO2019008157A1, [73]; WO2022147490A1; WO2022076556A2).They all describe the application of adeno-associated virus (AAV9) gene therapy using optimized polynucleotides encoding the fukutin-related protein.Specific constructs have also been studied to produce therapeutical and toxically acceptable levels of protein in the heart (WO2021053124A1).
Two clinical trials are in progress regarding gene therapy for FKRP-CDG (NCT05224505 and NCT05230459).Serum transferrin isoelectrofocusing (Tf IEF) is still the method of choice for screening N-glycosylation disorders associated with sialic acid deficiency.Initially, the test was introduced for the screening of chronic alcoholism.Serum transferrin is only N-glycosylated, and the bulk of it carries four sialic acids and, thus, four negative charges.Capillary zone electrophoresis is a valuable alternative screening method, but abnormal results have to be controlled by Tf IE [74] (US5993626A).

Diagnostic tools for CDG
As expected, many other serum glycoproteins besides transferrin show altered isoforms in CDG.Overall a wide range of methodologies has been explored and developed, such as the enzymatic derivatization of carbohydrate-deficient glycoproteins with fluoresceinylated monosaccharides and measurement of the fluorescence of the re-glycosylated glycoproteins (US5432059A), study of the interaction of glycoproteins with lectins or antibodies (WO0033076A1), and the MS or NMR of the specific peptide pattern obtained by enzymatic hydrolysis of the glycoprotein of interest (US2006216766A1).In addition, methods ensuring a higher sensitivity or a lesser sample handling have also been patented (such as WO0192890A1 and US8877454B2).
Another way to assess alterations of glycosylation profiles is the evaluation of the ratio of the amount of

US5432059A
Assay for glycosylation deficiency disorders (1995) The method of the invention relies on the enzymatic derivatization (by using sialyltransferases and galactosyltransferases) of carbohydrate-deficient glycoproteins in samples of body fluids obtained from subjects with metabolic disorders.In this way fluoresceinylated monosaccharides can be incorporated into the carbohydrate-deficient glycoprotein target.Fluorescence emission from the reglycosylated glycoprotein can be measured."The invention is based on the discovery that systems that include an affinity cartridge and a mass spectrometer are useful for detecting analytes such as transferrin, from a biological sample.When measuring CDTs, neuraminidase treated transferrin can be used as an internal standard, and can be applied to a membrane of affinity membrane cartridge, which is coated with antibodies having specific binding affinities for transferrin." Chronic alcoholism and carbohydrate-deficient glycoprotein syndrome, other inborn errors of metabolism EP3117217A1 WO2015135900A1 Analytical method for the identification of at least one glycoform of the transferrin protein ( "The invention refers to an analytical method for the identification of at least one transferrin glycoform and/ or isoform and/ or sialoform, and in particular of those known as carbohydrate-deficient transferrin, possibly present in a complex biological matrix, by protein functionalization with a source of lanthanide 3 + ion."

Carbohydrate-deficient transferrin glycoforms used as a diagnostic marker WO0033076A1 Diagnosis of human glycosylation disorders (2000)
The samples containing glycoconjugates are contacted with a diagnostic reagent that consists of a binding component (for example lectins, antibodies, etc.) and a label (such as fluorescent dyes, radiolabels, etc.).The ability of the diagnostic reagent to bind to the glycoconjugates in the sample is indicative of the presence or absence of the glycosylation disorder.

WO0192890A1
Methods for the analysis of picomole amounts of carbohydrates (2001) "The invention essentially overcomes the problems encountered in downscaling (miniaturizing) the analysis of underivatized carbohydrates and glycoconjugates to the subpicomole level." Carbohydrate Deficient Glycoprotein Syndromes US2006216766A1 Assay for protein isoforms (2004) The method relies on the use of a proteolytic enzyme that hydrolyses the protein of interest producing a specific peptide pattern that is characteristic of the glycosylation profile of the target protein.The fragments may be detected by methods which require the use of specific binding partners, or by chromatography, mass spectrometry, NMR, etc. "The invention provides an automatic oligosaccharide chain pre-treatment apparatus which is capable of performing purification at high speed and with high accuracy by automating processing steps." The profile of the whole serum N-glycan can distinguish CDG from healthy controls, and also certain subgroups of CDG from other subgroups of CDG US2014271615A1 Hyposialylation disorders (2014) The method includes measuring the ratio between the amount of monosialylated Thomsen-Friedenreich antigen and the amount of non-sialylated Thomsen-Friedenreich antigen in a biological sample (plasma or serum sample).The same measurement can be used for determining the effectiveness of a therapeutic agent."Glycosylation pathways comprising PGM3 substrates play a key role in regulating hematopoietic stem cells." "Mutations in Pgm3 cause a global reduction in UDP-GlcNAc levels and that despite the general importance of glycosylation in all cell types, incremental changes in UDP-GlcNAc levels selectively affect the modification of specific proteins, leading to a graded series of pathological changes." PGM3 has been identified "as an important mediator for the in vitro or in vivo regulation of cellular interactions and development, in particular of stem cells and their subsequent lineages." [76] Later, PGM3-CDG has been described as a severe infancy-onset immunodeficiency.[77,90,91] PGM3-CDG EP2905621A1 Means and methods for diagnosing and treating cdg caused by a deficiency of PGM1 (2015) PGM1 deficiency is a mixed CDG.An appropriate enzymatic test measures the activity on cell extracts.Effects associated with this defect have been described both in patients and in cell lines.Among others, the efficacy of galactose supplementation has been described.B4GALT1 may have a serine instead of an asparagine at the position 352.This p.Asn352Ser variant is protective against one or more cardiovascular conditions.B4GALT1 may be used to diagnose a patient's risk of developing cardiovascular conditions.

Table 4 (continued)
mono-sialylated to non-sialylated Thomsen-Friedenreich antigen in a biological sample, as described in US2014271615A1.Also, a specific method for simultaneous detection of α-DG and glycosylated α-DG for dystroglycanopathy patient biopsies has been patented (US2022291236A1).
Serum Tf IEF has some limitations; moreover, it is not a suitable biomarker for in vitro studies on cell models such as fibroblasts.Recently, polyols were identified as robust biomarkers of PMM2-CDG and several other CDG (WO2022103815A1).
However, genetic analysis is the most reliable diagnostic [75].
The discovery of the defect associated with carbohydrate-deficient glycoprotein syndrome type I or Jaeken disease, subsequently renamed PMM2-CDG, was patented in 1998 (WO9849324A2).Several glycoprotein and glycolipid metabolism enzymes were patented in 2002 (WO0236757A2).
PGM3 has long been considered a biomarker for forensic purposes.In 2006 it was described "as an important mediator for the in vitro or in vivo regulation of cellular interactions and development, in particular of stem cells and their subsequent lineages" (WO2006094344A1, [76]).PGM3 deficiency was first described in 2014 in patients with hyper-IgE syndrome phenotype characterized by recurrent infections, atopy, and elevated serum IgE [77,78].In 2015, PGM1-CDG was described at the clinical, biochemical and molecular levels, together with a possible therapeutic strategy based on the dietary supplementation of galactose (EP2905621A1, [79]).

Discussion
Among the most recent patents regarding drugs and therapeutic approaches, some led to clinical trials that are currently in progress, for example, epalrestat (NCT04925960), GLM101 (NCT05549219), and Adeno-Associated Virus vector carrying the human FKRP transgene (GNT0006, NCT05224505).Other patented drugs are still under development, such as the amide and urea derivatives that could act as pharmacological chaperones (EP3275863A1).
The commercialization of patented molecules is an exciting issue.To take a deeper insight, we focused on patents submitted by companies and screened the web to find information about the patent's follow-up.The number of newly commercialized drugs is meagre.Substrate replacement therapy with mannose-1-phosphate has been produced as GLM101 by Glycomine; it has received Orphan Drug Designation (ODD) in the US and Europe and Rare Pediatric Disease Designation (RPDD) in the US and is in clinical trial phase 2 (NCT05549219) [80].AT007, an aldose reductase inhibitor, is currently commercialized as the orphan drug Govorestat by Applied Therapeutics; Govorestat has not yet advanced in clinical trial for PMM2-CDG but is currently in clinical trial for different diseases (galactosemia, NCT04902781, and SORD Deficiency, NCT05397665) [81].
Repurposed drugs provide a different topic, being approved and then repositioned for CDG.For example, this is the case for Epalrestat, the first aldose reductase inhibitor patented by Perlara for use in PMM2-CDG (WO2020040831A1) and currently undergoing clinical trial phase 3.
Interestingly, many of these drugs derive from repositioning, a precious strategy in rare diseases [82][83][84].With this approach, knowing the patterns involved in the drug's action helps find different applications, either on known targets or off-targets [85][86][87].Serendipity is typical in drug repurposing, but on the other hand, data provided by 'omics' experiments contain information about the differential regulation of genes by specific treatments.For example, while investigating the effect of acetylsalicylic acid on Fabry patient-derived fibroblasts, Monticelli and co-workers recorded a strong down-regulation of the COG5 protein (0.103 ratio ASA/control [88]).
Blood tests for diagnosis are available, but molecular genetic testing represents the final diagnostic tool.Anyway, screening methods are not 100% reliable and even enzyme measurements could be debatable in mild cases, like in PMM2-CDG, but in many cases genetic results are not conclusive for the diagnosis and a biochemical or functional confirmation is essential for establishing the diagnosis.Therefore, the development of biomarkers, diagnostic and screening tools is of utmost importance.Many people with CDG are undoubtedly misdiagnosed [7], particularly those with mild or atypical phenotypes [89].
The CDG illustrate that incorrect glycosylation is associated with a bewildering broad phenotypic spectrum.However, the absence of a genotype-phenotype correlation shows the remarkable role of genomic variants in the development of the disease [26][27][28][29].In this regard, it is interesting to note that one of the patents concerns B4GALT1 and describes the protective effect of the p.Asn352Ser variant against one or more cardiovascular conditions (Table 3).
Our data clearly show the increasing interest in CDG by the Scientific Community.In the last few decades, many advances have been pursued.Nevertheless, besides the newly acquired knowledge, few drugs moved to clinical trials, and none of these has been approved, apart from the orphan drug designation.Among the reasons behind these data, the lack of funding for rare diseases is undoubtedly a significant issue [7].In our opinion, cooperation among the different stakeholder groups (i.e.researchers, clinicians, families and companies) would be a unique possibility to boost CDG research and reach the goal of approved therapies as soon as possible.

Conclusion
Our research on CDG patents identified 25 documents regarding drugs or therapeutic approaches, 17 regarding diagnostic tools and two regarding drug delivery tools.These patents (regarding numbers and specificities) can be considered indicators of the attention paid to the CDG and the success gained through clinical and research activities.

Fig. 1
Fig. 1 Classification of the patents derived from the research.For each class, the total number and the percentage are shown

Fig. 3
Fig. 3 Geographical distribution of patents' applicants.US: United States of America; AU, Australia; BE: Belgium; DE: Germany; ES: Spain; FR: France, GB: Great Britain; IT, Italy; JP: Japan; NO: Norway; SE, Sweden.For each country, the total number and the percentage are shown markers in PMM2-CDG.Patients with MAN1B1-CDG, ALG6-CDG, SLC39A8-CDG, MOGS-CDG, CDG type IIx, NANS-CDG, PIGS-CDG, and ALG8-CDG also demonstrated elevated levels of polyols.These biomarkers can be used to evaluate the efficacy of a treatment.

Table 2
Drugs/therapeutic approaches for CDG.

Table 3
Drugs delivery tools for CDG

Table 4
lists patents concerning diagnostic tools for CDG.

Table 4
Diagnostic tools for CDG Identification of genes involved in N-linked oligosaccharide synthesis in human ER.The function of the genes was obtained through complementation in yeast strains bearing a variants or deletions in the homologous genes.