DeCure for Autosomal dominant hypophosphatemic rickets
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant hypophosphatemic rickets — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAutosomal dominant hypophosphatemic rickets maps to a 4-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 autosomal dominant hypophosphatemic rickets 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
fibroblast growth factor 23 (FGF23) — FGF23 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 sulfoaminodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7YSH · 2.74 Å · ligand 2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose (SGN). Experimental structure, not a prediction.
What the evidence adds up to
X-linked hypophosphatemic rickets is the most common inherited form of rickets, caused by inactivating mutations in the PHEX gene and transmitted as an X-linked dominant disorder. A 2014 study of a sporadic Turkish girl aged 2 years with bowing of legs and growth retardation found a novel 13 bp deletion at the donor splice site of exon 5 of PHEX (c.663+12del). This deletion caused the spliceosome to use two nearby cryptic donor splice sites, producing two smaller transcripts that could not translate into functional proteins due to frameshift. Her parents did not carry the mutation, indicating a de novo event likely from mutagenesis of the X chromosome in paternal germ cells. She was treated with calcitriol 0.5 mg/kg/day and oral phosphate supplement with good response.
A 2024 case report from Pakistan describes a 14-month-old boy with stunted growth, limb abnormalities, and biochemical irregularities including elevated alkaline phosphatase and renal phosphate wasting. Radiographic assessments confirmed skeletal alterations typical of XLHR. Treatment involved phosphate supplementation alone because prior vitamin D injections had caused intoxication, so active vitamin D analogs were avoided. The report notes that management typically includes oral phosphate supplements and active vitamin D analogues, and mentions burosumab as a novel therapy targeting fibroblast growth factor 23, but does not provide any efficacy data for burosumab from this case. The authors state that some patients may require surgical correction for worsening skeletal deformities.
Earlier reviews from 2007 and 2019 describe the disorder as one of defective bone mineralization due to increased phosphate excretion accompanied by elevated phosphatonins like fibroblast growth factor 23. The 2007 review notes that identification of phosphatonins and genetic causes including PHEX, FGF23, the sodium-phosphate cotransporter NaPiIIc, and the bone matrix protein Dmp1 has opened the way to new treatment strategies, but gives no specific treatment outcomes. The 2019 review states that correct identification is important for determining therapy and that early diagnosis prevents subsequent complications, without reporting any trial results.
What is still missing are large, controlled trials comparing burosumab against conventional therapy with phosphate and vitamin D analogues, long-term outcome data on fracture rates and growth in treated patients, and studies that stratify patients by specific PHEX mutation type to see if response varies. The Pakistani case highlights that even standard treatment can be complicated by toxicity, and that access to genetic testing and awareness remain limited in many regions. No drug has been shown to normalise phosphate homeostasis or prevent all skeletal complications in a prospective trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Pediatrics · 2007 · 12 citations
Regulation of phosphate homeostasis in infants, children, and adolescents, and the role of phosphatonins in this process
AbstractPURPOSE OF REVIEW: Unlike calcium metabolism, the control of phosphate homeostasis has long been poorly understood. The identification of 'phosphatonins' in the serum of hypophosphatemic patients, the unveiling of the genetic causes of hypo and hyperphosphatemic diseases in patients, and the creation of finely adapted animal models have revolutionized our understanding of phosphate homeostasis. RECENT FINDINGS: Original reports published in 2006/2007 bring valuable pieces of information that enable better understanding of the physiological regulation of phosphate homeostasis by more precisely defining the interplay between PHEX, vitamin D, and phosphatonins; identification of new genes causing hypophosphatemic rickets, aside from PHEX and fgf23, namely the genes encoding for a renal sodium-phosphate cotransporter, NaPiIIc, and for a bone matrix protein, DmpI; and improved diagnosis of tumor-induced osteomalacia with more precise imaging techniques for tumor localization and more precise fibroblast growth factor 23 assays. SUMMARY: From a clinical point of view, these findings offer new tools for the diagnosis of hypophosphatemic rickets (biologic, genetic, imaging techniques) and open the way to new treatment strategies.
Journal of Pediatric Endocrinology and Metabolism · 2014 · 8 citations
Hypophosphatemic rickets caused by a novel splice donor site mutation and activation of two cryptic splice donor sites in the PHEX gene
AbstractX-linked hypophosphatemic rickets (XLH) is the most common inherited form of rickets. XLH is caused by inactivating mutations in the PHEX gene and is transmitted as an X-linked dominant disorder. We investigated PHEX mutation in a sporadic Turkish girl with hypophosphatemic rickets. The patient was 2 years of age with a complaint of inability to walk. She had bowing of legs and growth retardation. Laboratory data showed normal calcium, low phosphate with markedly elevated ALP, and low phosphate renal tubular reabsorption. She was treated with Calcitriol 0.5 mg/kg/day and oral phosphate supplement with good response. The entire coding region of PHEX gene was sequenced from patient's peripheral leukocyte DNA and a novel 13 bp deletion at the donor splice site of exon5 was found (c.663+12del). Instead of using the donor splice site of intron 4 to splice out exon 5 and intron 5, the spliceosome utilized two nearby cryptic donor splice sites (5' splice site) to splice out intron 4, resulting in two smaller transcripts. Both of them could not translate into functional proteins due to frameshift. Her parents did not carry the mutation, indicating that this is a de novo PHEX mutation likely resulting from mutagenesis of X chromosome in paternal germ cells. We conclude that c.663+12del is a novel mutation that can activate nearby cryptic 5' splice sites. The selection of cryptic 5' splice sites adds the complexity of cell's splicing mechanisms. The current study extends the database of PHEX mutation and cryptic 5' splice sites.
International Journal of Advances in Medicine · 2019 · 0 citations · open access
Rare cause of pathological fracture in adults as hypophosphatemic rickets
AbstractHypophosphatemic rickets is a disorder of defective bone minerlization due to defect in renal phosphate handling process. It is characterised by increased phosphate excretion accompanied by increased phosphatonins like fibroblast growth factor 23. It can be hereditary form of X linked, autosomal dominant, autosomal recessive type of hypophosphatemic rickets. It is associated with low serum phosphorus, normal serum calcium, inappropriately low to normal vitamin D level. Correct identification of these disorders is important for determining therapy. Early diagnosis and management prevent subsequent complication of the disease.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
PHEX GENE MUTATION IN A CHILD WITH X-LINKED HYPOPHOSPHATEMIC RICKETS
AbstractX-linked hypophosphatemic rickets is part of an extensive group of hereditary diseases characterized by loss of phosphate by the kidneys, which leads to growth disorders, rickets and osteomalacia. These conditions are characterized by a violation of the phosphate balance, which is necessary for the formation of bones.
Journal of Pediatrics Perinatology and Child Health · 2024 · 0 citations · open access
A Rare Case of Pediatric X-Linked Hypophosphatemic Rickets: Challenges and Insights from Pakistan
AbstractIntroduction and Importance: X-linked hypophosphatemic rickets (XLHR) is a rare hereditary disorder characterized by impaired phosphate metabolism, leading to skeletal deformities and growth retardation. XLHR prevalence rates vary globally, with limited data from Pakistan. This case report presents a 14-month-old boy from Pakistan with XLHR, detailing the clinical presentation, diagnostic approach, and management. Case Presentation: The individual displayed common symptoms of XLHR, such as stunted growth, limb abnormalities, and biochemical irregularities. Radiographic assessments confirmed skeletal alterations typical of XLHR. Treatment involved phosphate supplementation alone, as active vitamin D analogs were avoided due to prior vitamin D injections resulting in intoxication. Close monitoring and follow-up were implemented. Clinical Discussion: This case highlights the clinical features and management of XLHR in a Pakistani pediatric patient. Early recognition with radiographic imaging is crucial to identify distinct skeletal abnormalities and biochemical tests showing elevated alkaline phosphatase (ALP) and renal phosphate wasting. Molecular genetic testing confirms the diagnosis by detecting PHEX mutations. Management typically includes oral phosphate supplements and active vitamin D analogues varying on the case to counteract excess fibroblast growth factor 23 (FGF23) and Burosumab, a novel therapy targeting FGF23. Despite optimal medical management, some patients may require surgical correction for worsening skeletal deformities, with methods ranging from growth modulation techniques to more invasive procedures like osteotomies and fixation. Conclusion: This case highlights the challenges of recognising and reporting rare genetic disorders like X-linked hypophosphatemic rickets (XLHR) in Pakistan due to limited data and awareness. Improved access to genetic testing and increased awareness among healthcare professionals is crucial for better management and support for affected individuals and families, ultimately improving outcomes and quality of life.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
