Frequency of Ectopic Calcifications Among Patients With Hypophosphatasia in the Global HPP Registry
Bibliographic record
Abstract
Abstract Ectopic calcifications have been observed in patients with hypophosphatasia (HPP)—a rare, inherited, metabolic disorder characterized by reduced enzymatic activity of tissue nonspecific alkaline phosphatase. The natural history of these calcifications is poorly understood. Using data from the Global HPP Registry, a cross-sectional, observational analysis was conducted to better understand the prevalence of nephrocalcinosis and eye calcifications in patients with HPP in the absence of treatment with the enzyme replacement therapy, asfotase alfa. The association between hypercalcemia (serum calcium ≤10.3 mg/dL [normal]; 10.4–11.9 mg/dL [mild hypercalcemia]; ≥12.0 mg/dL [moderate to severe hypercalcemia]) and ectopic calcification was also evaluated. Of the patients in the study population with renal ultrasound data (n=327), 11.0% had nephrocalcinosis; no patients had severe nephrocalcinosis. In children (aged <18 years; n=174), 13.2% had nephrocalcinosis, and the median age at the first diagnosis of nephrocalcinosis was 4 years (range: 0–17 years). In adults (aged ≥18 years; n=153), 8.5% had nephrocalcinosis, and the median age at the first diagnosis of nephrocalcinosis was 52 years (range: 27–72 years). Data on serum calcium levels were available for 318 patients with renal ultrasounds. Of these patients, 73 patients (23.0%) had a history of hypercalcemia, of whom 10 (13.7%; children: n=9; adults: n=1) also had nephrocalcinosis. In patients with moderate to severe hypercalcemia (n=7), 6 patients (85.7%) were diagnosed with nephrocalcinosis; the majority (68.8%) of patients with nephrocalcinosis did not have a documented history of hypercalcemia. Of the patients who had ophthalmological assessments (n=137), 6 patients (4.4%) had eye calcifications; no patients had moderate or severe eye calcifications. The median age at the first diagnosis of eye calcifications was 16 years (range: 15–16 years) in children and 51 years (range: 30–57 years) in adults. Data on serum calcium levels were available for 80 patients with ophthalmological assessments. Coexistence of eye calcifications and reported hypercalcemia was observed in only 3 of these patients, all of whom had mild hypercalcemia; the remaining 3 patients with eye calcifications exhibited no hypercalcemia. No patients in this analysis presented with both nephrocalcinosis and eye calcifications. These results indicate that the prevalence of ectopic calcifications in patients with HPP is low during the natural course of the disease, with nephrocalcinosis being more common than eye calcifications. In addition, the higher prevalence of nephrocalcinosis in patients with moderate to severe hypercalcemia suggests that very high serum calcium may be a risk factor in some patients. Future studies are needed to assess the impact of treatment with asfotase alfa on ectopic calcifications in patients with HPP.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".