Enhancing Newborn Screening for Tyrosinemia Type I
Bibliographic record
Abstract
Hepatorenal tyrosinemia, also known as tyrosinemia type I (Tyr-I) is an autosomal recessive inborn error of metabolism. The primary enzyme defect has been attributed to a deficiency of fumarylacetoacetase (EC 3.7.1.2)(1). Tyr-I is usually asymptomatic in newborns, but if left untreated it affects liver, kidney, bone, and peripheral nerves; in its most severe form, affected infants may die from liver failure in the first months of life(2). The majority of Tyr-I patients can be treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) with promising outcomes(3)(4). The incidence of this condition is estimated to be 1:100 000 but may be much higher in certain populations such as the province of Quebec, where it occurs once in every 20 000 live births(5). Given the effectiveness of treatment and a test for its marker in the Guthrie specimen, Tyr-I fulfills the criteria for newborn screening and is included in the American College of Medical Genetics’ core panel of newborn screening recommendations(6). Most newborn screening programs detect Tyr-I by measurement of tyrosine in Guthrie specimens (dried blood spot)(7)(8)(9). This method is convenient because tyrosine can be extracted and monitored along with other amino acids and acylcarnitines present in newborn screening panels(7)(8)(9). It has become clear, however, that tyrosine alone is an inadequate marker for screening of Tyr-I because tyrosine measurement lacks specificity and cannot distinguish Tyr-I from other disorders in tyrosine catabolism and transient hypertyrosinemia(10)(11). Even more disconcerting are reports of missed cases of Tyr-I in newborns with …
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".