DeCure for ALG8-congenital disorder of glycosylation
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for ALG8-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 moduleALG8-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 alg8-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 2009 a new case of ALG8 deficiency (CDG Ih) was reported in a girl born at 29 weeks. She had generalised oedema, multifocal myoclonic seizures, and bleeding from combined coagulopathy from the first day. Diarrhoea progressed to protein-losing enteropathy with ascites and pericardial effusion in the third week. Pharmacoresistant seizures and cortical, cerebellar and optic nerve atrophy were present. No liver disease except coagulopathy was observed, but steatofibrosis with cholestasis was found at autopsy. She died at two months from progressive oedema, bleeding and cardio-respiratory insufficiency. Two heterozygous mutations were found in ALG8: c.139A>C (p.T47P) and the novel c.1090C>T (p.R364X). The authors concluded that prognosis is unfavourable and that most affected children have early onset with heterogeneous symptoms including multiple organ dysfunction, coagulopathy and protein-losing enteropathy.
Two unrelated patients with ALG11-CDG were described in 2019. Both had severe psychomotor disabilities and epilepsy. Their fibroblasts synthesised truncated precursor glycan structures consistent with ALG11-CDG and showed hypoglycosylation of the biomarker GP130. One patient had a normal transferrin glycosylation profile, which had not been reported before in ALG11-CDG. The authors expanded the clinical and mutational spectrum of the condition.
In 2025 three new cases of ALG1-CDG from Iran were reported, all bearing a novel homozygous variant p.Leu375Gln. All three had seizures at a young age and developmental delays, with speech and learning disabilities. One had cerebral atrophy. All had walking problems, but the youngest gained the ability to walk with occupational therapy. All survived to childhood and adulthood, which the authors described as a mild phenotype. Diagnosis was established by whole exome sequencing after several years of delay. The variant’s pathogenic effect was assessed computationally with SIFT, Poly-Phen2 and Mutation Taster, and protein homology modelling was performed.
No drug treatment was tested or proposed in any of these three abstracts. What is missing for ALG8, ALG11 and ALG1-CDG is any clinical trial of a therapy, any systematic patient registry large enough to stratify by genotype or severity, and any funding directed at repurposing or drug screening for these ultra-rare glycosylation disorders.
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 · 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.
Journal of Inherited Metabolic Disease · 2009 · 25 citations · open access
A new case of ALG8 deficiency (CDG Ih)
AbstractUNLABELLED: Congenital disorders of glycosylation (CDG) represent an expanding group of inherited diseases. One of them, ALG8 deficiency (CDG Ih), leads to protein N-glycosylation defects caused by malfunction of glucosyltransferase 2 (Dol-P-Glc:Glc1-Man(9)-GlcNAc(2)-P-P-Dol glucosyltransferase) resulting in inefficient addition of the second glucose residue onto lipid-linked oligosaccharides. So far, only five patients have been described with ALG8 deficiency. We present a new patient with neonatal onset. The girl was born at the 29th week of gestation complicated by oligohydramnios. Although the early postnatal adaptation was uneventful (Apgar score 8 and 9 at 5 and 10 min), generalized oedema, multifocal myoclonic seizures, and bleeding due to combined coagulopathy were present from the first day. Diarrhoea progressing to protein-losing enteropathy with ascites and pericardial effusion developed in the third week of life. Pharmacoresistant seizures and cortical, cerebellar and optic nerve atrophy indicated neurological involvement. No symptoms of liver disease except coagulopathy were observed; however, steatofibrosis with cholestasis was found at autopsy. The girl died at the age of 2 months owing to the progressive general oedema, bleeding and cardio-respiratory insufficiency. Molecular analysis revealed two heterozygous mutations in the ALG8 gene: c.139A>C (p.T47P) and the novel mutation c.1090C>T (p.R364X). CONCLUSION: The prognosis of patients with ALG8 deficiency is unfavourable. The majority of affected children have early onset of the disease with heterogeneous symptoms including multiple organ dysfunction, coagulopathy and protein-losing enteropathy. Neurological impairment is not a general clinical symptom, but it has to be taken into consideration when thinking about ALG8 deficiency.
American Journal of Medical Genetics Part A · 2019 · 15 citations · open access
ALG11‐CDG syndrome: Expanding the phenotype
AbstractALG11-Congenital Disorder of Glycosylation (ALG11-CDG, also known as congenital disorder of glycosylation type Ip) is an inherited inborn error of metabolism due to abnormal protein and lipid glycosylation. We describe two unrelated patients with ALG11-CDG due to novel mutations, review the literature of previously described affected individuals, and further expand the clinical phenotype. Both affected individuals reported here had severe psychomotor disabilities and epilepsy. Their fibroblasts synthesized truncated precursor glycan structures, consistent with ALG11-CDG, while also showing hypoglycosylation of a novel biomarker, GP130. Surprisingly, one patient presented with normal transferrin glycosylation profile, a feature that has not been reported previously in patients with ALG11-CDG. Together, our data expand the clinical and mutational spectrum of ALG11-CDG.
Cutaneous Findings in Congenital Disorders of Glycosylation: The Hanging Fat Sign
AbstractThe congenital disorders of glycosylation are a group of rare metabolic disorders with predominantly neurologic findings. Some variants of this disorder also exhibit cutaneous manifestations. We report a patient with a congenital disorder of glycosylation type Ia, the most common form, with emphasis on the cutaneous findings of this type, and summarize the cutaneous findings in the other forms of the disorder.
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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