A Novel Citrin Deficiency Mutation in a Cholestatic Infant
Bibliographic record
Abstract
To the Editor: Although certain causes of neonatal cholestasis, such as biliary atresia, are well known and promptly excluded, the cholestasis differential is vast, including numerous, less well-recognized genetic-metabolic disorders. Physicians need to be aware of this important disease category owing to significant health implications and potential interventions. As an example, we evaluated a cholestatic infant eventually found to have a novel citrin deficiency mutation. The patient, a term Chinese girl with elevated citrulline on the Quebec newborn urinary screen, was admitted at 2 months for progressive jaundice. Investigations revealed cholestasis, transaminitis, positive urinary reducing substances, coagulopathy, elevated ammonia and lactate, and low glucose. Plasma amino acid determination showed increased citrulline, threonine, serine (with elevated threonine-to-serine ratio), methionine, tyrosine, and arginine, with similar urinary elevations. Alpha-fetoprotein was measured only at 8 months (normal). SLC25A13 gene analysis revealed a paternally inherited known deleterious mutation reported in type II citrullinemia, c.1638_1660dup23 (p.A554GfsX16) (1), and 2 maternally inherited heterozygous novel unclassified variants, c.1046T>C (p.I349T) and c.1067T>A (p.M356K). The highly conserved nature of the amino acids in these variants suggested deleteriousness. The patient responded promptly to a galactose-free, low-carbohydrate, and protein-/lipid-rich diet; within 1 week, citrulline, bilirubin, and liver enzymes dropped substantially and normalized by 6 months. Although most common in east Asia, citrin deficiency is recognized to be panethnic. (2) It is an important consideration in the cholestatic infant, even in North America. Physicians need to include basic metabolic investigations, namely plasma amino acids, urine organic acids, and acylcarnitine profile in the evaluation of neonatal cholestasis. Acknowledgment The authors thank the patient's parents for allowing their child to be featured.
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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 | 0.006 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.008 | 0.005 |
| Insufficient payload (model declined to judge) | 0.002 | 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".