Rifampin monotherapy for children with idiopathic infantile hypercalcemia
Bibliographic record
Abstract
Idiopathic Infantile Hypercalcemia (IIH) is characterized by hypercalcemia and hypercalciuria owing to PTH-independent increases in circulating concentrations of 1,25(OH)2D. At least 3 forms of IHH can be distinguished genetically and mechanistically: infantile hypercalcemia-1 (Hypercalcemia, Infantile, 1; HCINF1) due to CYP24A1 mutations results in decreased inactivation of 1,25(OH)2D; HCINF2 due to SLC34A1 mutations results in excessive 1,25(OH)2D production; and HCINF3 in which a variety of gene variants of uncertain significance (VUS) have been identified and where the mechanism for increased 1,25 (OH)2D is unclear. Conventional management with dietary calcium and vitamin D restriction has only limited success. Induction of the P450 enzyme CYP3A4 by rifampin can provide an alternate pathway for inactivation of 1,25(OH)2D that is useful in HCINF1 and may be effective in other forms of IIH. We sought to assess the efficacy of rifampin to decrease levels of serum 1,25(OH)2D and calcium, and urinary calcium concentrations in subjects with HCINF3, and to compare the response to a control subject with HCINF1. Four subjects with HCINF3 and the control subject with HCINF1 completed the study using rifampin 5 mg/kg/day and 10 mg/kg/day each for 2 months separated by a 2-month washout period. Patients had age-appropriate intake of dietary calcium plus 200 IU vitamin D/day. Primary outcome was efficacy of rifampin to lower serum concentrations of 1,25(OH)2D. The secondary outcomes included the reduction of serum calcium, urinary calcium excretion (as random urine calcium: creatinine (ca:cr) ratio) and serum 1,25(OH)2D/PTH ratio. Rifampin was well tolerated and induced CYP3A4 at both doses in all subjects. The control subject with HCINF1 showed significant response to both rifampin doses with decreases in the serum concentration of 1,25(OH)2D and the 1,25(OH)2D/PTH ratio while the serum and urine ca:cr levels were unchanged. The four patients with HCINF3 showed reductions in 1,25(OH)2D and urinary ca:cr after 10 mg/kg/d, but hypercalcemia did not improve and there were variable responses in 1,25(OH)2D/PTH ratios. These results support further longer-term studies to clarify the usefulness of rifampin as a medical therapy for IIH.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".