DeCure for ALG3-congenital disorder of glycosylation
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for ALG3-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 moduleALG3-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 alg3-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.
What the evidence adds up to
In a retrospective review of Saudi patients, 7 out of 27 individuals with congenital disorders of glycosylation had ALG3-CDG, all with homozygous gene mutations. The combined carrier frequency of CDG for the encountered founder mutations in the Saudi population was 11.5 per 10,000, translating to a minimum disease burden of 14 patients per 1,000,000. No treatment outcomes specific to ALG3-CDG were reported in that study.
A 2021 review states that treatment options for congenital disorders of glycosylation remain limited and are often constrained to symptomatic management of disease manifestations. The review notes recent advances in therapies aimed at the causative defect and secondary disease manifestations, but it does not provide specific efficacy data for any drug in ALG3-CDG.
No abstract in this set reports a drug trial, response rate, or survival data for ALG3-CDG. The 2025 report on ALG1-CDG, a related but distinct subtype, describes three cases with a novel homozygous variant who survived to childhood and adulthood with a mild phenotype, but it offers no treatment intervention data. What is still missing for ALG3-CDG specifically are any published clinical trials, any tested pharmacological intervention, and any patient stratification strategy that might identify who could benefit from a repurposed drug.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics Part A · 2017 · 41 citations
Congenital disorders of glycosylation: The Saudi experience
AbstractWe retrospectively reviewed Saudi patients who had a congenital disorder of glycosylation (CDG). Twenty-seven Saudi patients (14 males, 13 females) from 13 unrelated families were identified. Based on molecular studies, the 27 CDG patients were classified into different subtypes: ALG9-CDG (8 patients, 29.5%), ALG3-CDG (7 patients, 26%), COG6-CDG (7 patients, 26%), MGAT2-CDG (3 patients, 11%), SLC35A2-CDG (1 patient), and PMM2-CDG (1 patient). All the patients had homozygous gene mutations. The combined carrier frequency of CDG for the encountered founder mutations in the Saudi population is 11.5 per 10,000, which translates to a minimum disease burden of 14 patients per 1,000,000. Our study provides comprehensive epidemiologic information and prevalence figures for each of these CDG in a large cohort of congenital disorder of glycosylation patients.
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.
American Journal of Medical Genetics Part A · 2007 · 37 citations
CDG‐Id in two siblings with partially different phenotypes
AbstractWe present two sibs with congenital disorder of glycosylation (CDG) type Id. Each shows severe global delay, failure to thrive, seizures, microcephaly, axial hypotonia, and disaccharidase deficiency. One sib has more severe digestive issues, while the other is more neurologically impaired. Each is compound heterozygous for a novel point mutation and an already known mutation in the ALG3 gene that leads to the synthesis of a severely truncated oligosaccharide precursor for N-glycans. The defect is corrected by introduction of a normal ALG3 cDNA. CDG should be ruled out in all patients with severe seizures and failure to thrive. (c) 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A · 2015 · 24 citations
ALG3‐CDG: Report of two siblings with antenatal features carrying homozygous p.Gly96Arg mutation
AbstractCongenital disorders of glycosylation (CDG) are a group of inborn errors of metabolism presenting with heterogeneous multisystemic clinical manifestations. To date, more than 60 different types of CDG have been reported. ALG3-CDG is very rare, with only nine patients described so far. We report two affected siblings presenting prenatally with skeletal abnormalities associated with dysmorphic features, cerebellar vermis hypoplasia, corpus callosum agenesis, hepatic fibrosis and poor prognosis. This is the first detailed report of an affected fetus including clinical, radiographic and pathological findings. The patients showed some clinical features previously unreported in ALG3-CDG, such as bone dysplasia, cataract, corneal opacities, and pons hypoplasia. Both patients were homozygous for the previously unreported p.Gly96Arg mutation of the ALG3 gene. One patient showed chondrodysplasia punctata (CDP), which has not been previously reported in CDG. An exhaustive genetic and metabolic assessment, performed in order to rule out other possible causes of CDP, showed abnormally raised levels of anti-nuclear antibodies in the mother who, nevertheless, did not show any clinical sign of autoimmune disease during a 7 years follow-up. We speculate that the observed CDP may be explained by the maternal anti-nuclear antibodies; alternatively, a possible link to the underlying metabolic disorder cannot be ruled out. In conclusion, we report the clinical, pathological, biochemical and molecular characterization of two further patients affected by ALG3-CDG, expanding the phenotypic spectrum of this very rare disease.
Lethal COG6‐CDG in neonatal patient with arachnodactyly, joint contractures, and skin manifestations: Founder mutation in the Southeastern European population?
AbstractHerein, we report a lethal case of the ultra-rare COG6-congenital disorder of glycosylation (CDG) presenting with skin manifestations (scaling and erosions) and joint contractures in a neonate of Albanian origin. The patient was homozygous for a COG6 pathogenic variant, previously reported in another three individuals of Greek, Bulgarian and Turkish descent. The presence of a founder mutation in the geographical area is possible. The index case emphasizes the need to consider CDGs in neonatal patients with skin manifestations and joint contractures, particularly patients of Southeastern European or West Asian origin.
Egyptian Journal of Medical Human Genetics · 2025 · 1 citations · open access
ALG1-congenital disorder of glycosylation: report of clinical and genetic features of three new cases and review of literature
AbstractAbstract Background The ALG1-congenital disorder of glycosylation condition is a rare autosomal recessive disorder with approximately 80 patients reported worldwide up to now. This disorder is caused by a deficiency of β1,4 mannosyltransferase due to the pathogenic variants within the ALG1 gene which leads to impaired protein glycosylation. This disorder usually causes multiorgan damage. This is the first report of ALG1-CDG cases from Iran who are bearing a novel variant in a homozygote state. Case presentation The clinical and molecular features of three cases have been described. All three cases in this study had experienced seizures at a young age and had developmental delays. They were suffering from speech and learning disabilities, and in one case, cerebral atrophy was also present. Although they all had walking problems, the youngest case gained the ability to walk by occupational therapy. Additionally, they all survived to childhood and adulthood which indicates a mild phenotype. Despite several years of delayed diagnosis, a novel variant p.Leu375Gln was identified in the cases in homozygous form through whole exome sequencing, which ultimately established a diagnosis. The pathogenic effect of the novel variant was assessed computationally. It has been evaluated using prediction tools including SIFT, Poly-Phen2, and Mutation taster. The protein homology modeling was performed, and the variant effect on hydrogen bonds and protein stability was assessed. Conclusion The findings of this study expand our knowledge of clinical and genetic features of ALG1-CDG and present the significant role of next-generation sequencing technologies in the diagnosis of rare disorders.
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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