Aortic Xanthomatosis With Coronary Ostial Occlusion in a Child Homozygous for a Nonsense Mutation in <i>ABCG8</i>
Bibliographic record
Abstract
A 5-year-old girl with a recent history of recurrent abdominal pain presented with acute respiratory distress that rapidly became asystolic.She then could not be revived.At autopsy, widespread yellow aortic xanthomas were seen, with severe atheromatous narrowing of both coronary ostia (Figure 1).The right and left anterior descending arteries showed focal marked atheromatous narrowing.Grossly and microscopically, there were no specific myocardial changes.Atheromas were also seen on the surfaces of the mitral valve leaflets and within the pulmonary artery.Aortic lesions extended to the level of the superior mesenteric artery, and atheromas were present in the branches of the aortic arch.Serum cholesterol concentration from a sample of post-mortem blood was 13.0 mmol/L (503 mg/dL).Parental lipoprotein profiles were relatively normal.Genomic DNA was isolated from frozen liver, and sequencing of the LDLR, APOB, ARH, and ABCG5 genes revealed no mutations.However, a novel CϾG mutation was found at the second residue of codon nucleotide 107 in exon 3 of the ABCG8 gene, which predicted premature truncation of the protein product (S107X) (Figure 2).This mutation was absent from 400 normal chromosomes.The diagnosis of sitosterolemia, a rare autosomal recessive disorder of sterol absorption, was confirmed by documenting elevated serum total cholesterol and sitosterol concentrations in her sister, brother, and female cousin, aged 5, 4, and 8 years, respectively.Serum cholesterol was 10.8, 11.8, and 9.2 mmol/L (416, 455, and 356 mg/dL), respectively, and serum sitosterol concentrations were 282, 447, and 184 mg/L, respectively (reference range 0 to 10 mg/L) in these relatives, who were also shown to be homozygotes for S107X.The use of bile acid binding resins has greatly improved the lipoprotein profile in the 3 surviving homozygotes.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".