DeCure for B4GALT1-congenital disorder of glycosylation
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for B4GALT1-congenital disorder of glycosylation — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleB4GALT1-congenital disorder of glycosylation maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for b4galt1-congenital disorder of glycosylation is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
beta-1,4-galactosyltransferase 1 (B4GALT1) — B4GALT1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet pgedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2FY7 · 1.7 Å · ligand TRIETHYLENE GLYCOL (PGE). Experimental structure, not a prediction.
What the evidence adds up to
For B4GALT1-congenital disorder of glycosylation, only three patients with two different mutations had been reported before 2020. A 2020 study identified three additional patients from one extended pedigree, all homozygous for a novel mutation in B4GALT1 — the first disease-causing variant found in the gene’s transmembrane domain. These patients showed a uniform clinical picture of intellectual disability, marked pancytopenia requiring chronic management, and novel features including pulmonary hypertension and nephrotic syndrome. Two of the three patients had a normal pattern of transferrin glycosylation on repeated analysis, despite a moderate elevation of Man3GlcNAc4Fuc1 on serum N-glycan analysis.
Broader reviews of congenital disorders of glycosylation (CDG) from 2021 and 2024 state that treatment options remain limited and are mostly confined to managing symptoms rather than correcting the underlying defect. The same reviews note that some novel therapies have moved from bench to bedside in recent years, but they do not name any specific drug or intervention that has been tested in B4GALT1-CDG. A 2024 case series describes four patients diagnosed with CDG type 2 who presented with hemolytic anaemia and prolonged jaundice, but those patients had mutations in the GSS gene, not B4GALT1, and the report does not address treatment outcomes.
No controlled trial, no quantitative efficacy data, and no drug repurposing evidence exist for B4GALT1-CDG. What is missing is any dedicated clinical trial, any financial commitment to drug screening or development for this ultra-rare subtype, and any systematic effort to stratify patients by mutation type or glycosylation pattern.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Frontiers in Genetics · 2021 · 41 citations · open access
Treatment Options in Congenital Disorders of Glycosylation
AbstractDespite advances in the identification and diagnosis of congenital disorders of glycosylation (CDG), treatment options remain limited and are often constrained to symptomatic management of disease manifestations. However, recent years have seen significant advances in treatment and novel therapies aimed both at the causative defect and secondary disease manifestations have been transferred from bench to bedside. In this review, we aim to give a detailed overview of the available therapies and rising concepts to treat these ultra-rare diseases.
Clinical Genetics · 2020 · 15 citations · open access
B4GALT1‐congenital disorders of glycosylation: Expansion of the phenotypic and molecular spectrum and review of the literature
AbstractA congenital disorder of glycosylation due to biallelic mutations in B4GALT1 has been previously reported in only three patients with two different mutations. Through homozygosity mapping followed by segregation analysis in an extended pedigree, we identified three additional patients homozygous for a novel mutation in B4GALT1, expanding the phenotypic spectrum of the disease. The patients showed a uniform clinical presentation with intellectual disability, marked pancytopenia requiring chronic management, and novel features including pulmonary hypertension and nephrotic syndrome. Notably, affected individuals exhibited a moderate elevation of Man3GlcNAc4Fuc1 on serum N-glycan analysis, yet two of the patients had a normal pattern of transferrin glycosylation in repeated analysis. The novel mutation is the third disease-causing variant described in B4GALT1, and the first one within its transmembrane domain.
Molecular Genetics and Metabolism · 2024 · 12 citations · open access
Treatment of congenital disorders of glycosylation: An overview
AbstractWhile the identification and diagnosis of congenital disorders of glycosylation (CDG) have rapidly progressed, the available treatment options are still quite limited. Mostly, we are only able to manage the disease symptoms rather than to address the underlying cause. However, recent years have brought about remarkable advances in treatment approaches for some CDG. Innovative therapies, targeting both the root cause and resulting manifestations, have transitioned from the research stage to practical application. The present paper aims to provide a detailed overview of these exciting developments and the rising concepts that are used to treat these ultra-rare diseases.
Hematology Transfusion and Cell Therapy · 2024 · 0 citations · open access
CLINICAL AND GENETIC FEATURES IN CONGENITAL GLYCOSATION DEFECTS PRESENTING WITH HEREDITARY HEMOLYTIC ANEMIA AND PROLONGED JAUNDICE
AbstractCongenital glycosylation disorders (CGD) are a large group of genetic diseases that occur due to a decrease or increase in the glycosylation of glycoconjugates. Congenital glycosylation disorders; They can be grouped under 4 groups: protein N-glycosylation, protein O-glycosylation, combined N- and O-glycosylation and lipid glycosylation disorders. Congenital glycosylation disorders are divided into 2 main groups: Type I and II (CGB-1 and GB-2). In this article, we would like to present a cases of CGB with an atypical presentation, presenting clinical findings with hemolytic anemia and prolonged jaundice, and diagnosed by clinical exon panel genetic study, since it is very rare in the literature. Our first patient, H1, was a 6-month-old male infant who received erythrocyte transfusion at an external center at the age of 14 days due to jaundice and anemia during the neonatal period (when HB: 5 g/dl), and then applied to the pediatric hematology clinic of our hospital with the same complaints at the age of 43 days. As a result of molecular tests, he was diagnosed with CGD type 2. Our other patient, H2, is a 10-year-old male, our third patient, H3, is a 13-year-old male, and our last patient, H4, is a 17-year-old male; These 3 patients were siblings. All three of them were hospitalized at an external center with jaundice and anemia during the neonatal period, but after diagnostic genetic tests, H4 was diagnosed after 3 years of age, but the other siblings were diagnosed after 6 months of age due to the oldest sibling's history. C.657c>A homozygous mutation was detected in the GSS gene in these siblings. The diagnostic difficulties and treatment options of 4 patients (H1, H2, H3, H4), who received inpatient treatment with anemia and jaundice in the pediatric hematology clinic between 2022 and 2024 and were ultimately diagnosed with CGD, were obtained from the hospital information processing system and presented because they are very rare in the literatüre. Our first patient, H1, was a 6-month-old male infant who received erythrocyte transfusion at an external center at the age of 14 days due to jaundice and anemia during the neonatal period (when HB: 5 g/dl), and then applied to the pediatric hematology clinic of our hospital with the same complaints at the age of 43 days. As a result of molecular tests, he was diagnosed with CGD type 2. Our other patient, H2, is a 10-year-old male, our third patient, H3, is a 13-year-old male, and our last patient, H4, is a 17-year-old male; These 3 patients were siblings. All three of them were hospitalized at an external center with jaundice and anemia during the neonatal period, but after diagnostic genetic tests, H4 was diagnosed after 3 years of age, but the other siblings were diagnosed after 6 months of age due to the oldest sibling's history. C.657c>A homozygous mutation was detected in the GSS gene in these siblings. Although prolonged jaundice and anemia are quite common, we wanted to emphasize with this very unique study that metabolic diseases may be among the differential diagnoses that are very rare in the literature. CGD has been diagnosed in only 40 cases in the last 30 years; Diagnostic evaluation with genetic consultation is very important for diagnosis. Literature data on rare diseases will be strengthened with new studies.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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