New Mutation Affecting Hypoxanthine Phosphoribosyltransferase Responsible for Severe Tophaceous Gout
Bibliographic record
Abstract
To the Editor: Hypoxanthine phosphoribosyltransferase (HPRT) deficiency, which is due to mutations of the HPRT1 gene, is a rare cause of inherited hyperuricemia and gouty arthritis1. Different HPRT1 mutations induce various levels of residual HPRT enzymatic activity, resulting in clinical symptoms of various severity2. Complete HPRT deficiency leads to the classic clinical phenotype of Lesch-Nyhan disease (LND), characterized by uric acid overproduction and its sequelae (nephrolithiasis, gout, and tophi), motor dysfunction, and behavioral problems including recurrent self-injury3. However, there also are attenuated clinical variants in which some of these clinical features are either absent or clinically insignificant. Collectively, patients with attenuated phenotypes are designated Lesch-Nyhan variants (LNV)4. The mildest form of LNV includes only overproduction of uric acid and its associated problems. These patients do not have clinically overt neurological or behavioral abnormalities, and most often are described as having HPRT-related hyperuricemia (HRH). Between the 2 extreme phenotypes of LND and HRH is a spectrum of phenotypes with varying degrees of neurological abnormalities, designated HPRT-related neurological dysfunction (HRND). Patients with HRND have an overproduction of uric acid along with some neurological difficulties, but they do not exhibit the self-injurious behaviors seen in classic LND. Patients with LND or LNV have both increased monosodium urate monohydrate (MSU) crystal formation that leads to gouty arthritis and arthropathy, tophi, and/or nephrolithiasis4,5,6. The gout resulting from HPRT deficiency is remarkable in its severity and its propensity to form tophi5,6. Its juvenile onset in a male is an important diagnostic clue for HPRT deficiency. The discovery of more than 600 mutations in the HPRT1 gene and their … Address correspondence to Dr. I. Ceballos-Picot, Laboratoire de Biochimie métabolique, Hôpital Necker-Enfants malades, 149 rue de Sèvres, 75015 Paris, France. E-mail: irene.ceballos{at}nck.aphp.fr
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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 | 0.004 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.009 | 0.006 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".