Reclassification of Hypophosphatemic Bone Disease as X-Linked Hypophosphatemia Following Genetic Testing in Adulthood
Bibliographic record
Abstract
Background: X-linked hypophosphatemia (XLH) is a disorder caused by a pathogenic variant in the phosphate-regulating endopeptidase homolog X-linked gene. This leads to increased fibroblast growth factor 23 synthesis, prompting renal phosphate wasting and hypophosphatemia. Adults with XLH present with osteomalacia, chronic musculoskeletal pain, enthesopathy, osteoarthritis, fractures, and pseudofractures. We present a patient initially diagnosed with hypophosphatemic, nonrachitic bone disease. However, later genetic testing identified a pathogenic phosphate-regulating endopeptidase homolog X-linked variant (c.1645+1G>A), establishing an XLH diagnosis. Case Report: A 50-year-old male was diagnosed with XLH through molecular testing at age 49. He was initially diagnosed at age 3 years with hypophosphatemic bone disease due to an unclear inheritance pattern. Treatment with phosphate and active vitamin D was started but discontinued at age 13 due to adverse effects, then resumed between ages 30 and 45. The patient presented with joint pain, abnormal gait, dental abscesses, and right hip replacement due to early-onset osteoarthritis with history of an atraumatic vertebral fracture at age 42. Labs showed hypophosphatemia, low tubular phosphate reabsorption, and elevated alkaline phosphatase and fibroblast growth factor 23. He was switched to burosumab therapy, resulting in clinical improvement. Discussion: This case underscores the diagnostic challenges of atypical XLH, particularly when X-linked inheritance patterns are absent. It illustrates the transformative role of molecular diagnostics in establishing diagnoses. It also reports on the impact of burosumab therapy when initiated in adults. Conclusion: This case demonstrates hallmark biochemical and radiological features of XLH, and the value of genetic testing in establishing a definitive diagnosis, particularly in individuals with atypical or nonclassical presentations.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".