A338 LYSOSOMAL ACID LIPASE DEFICIENCY (LAL-D): FROM DIAGNOSIS TO THERAPY IN CANADA
Bibliographic record
Abstract
Lysosomal Acid Lipase (LAL-D) deficiency is an ultra-rare lysosomal storage disorder. Clinical features in the late-onset form include dyslipidemia (elevated LDL, low HDL), elevated liver enzymes, hepatomegaly, and splenomegaly. This can progress to liver fibrosis and cirrhosis. LAL-D is caused by deficient activity of the LAL enzyme, resulting in the accumulation of cholesteryl esters and triglycerides throughout the body, predominately in the liver, spleen, gastrointestinal tract, and blood vessel walls. Supportive management with lipid-modifying agents, hematopoietic stem cell and liver transplant has been tried without major success. We describe our centre’s experience of 3 patients with LAL-D. We describe our preliminary experience in treating this condition with Enzyme Replacement therapy (Sebelipase Alfa Kanuma®) Over the last 20 years, we have had three patients with a confirmed diagnosis of LAL-D. Two adult patients, currently 31 and 40 years old, were diagnosed at 11y and 14 y with LAL activities at about 7% of control mean using fibroblasts and peripheral blood leukocytes after presenting with hepatosplenomegaly. Both adult patients were lost to follow up. A nine year old girl of French and Welsh background presented in 2014 with hepatomegaly, elevations in liver enzymes and dyslipidemia - high total cholesterol 7.4 mmol/L, high LDL cholestrol (4.7) mmol/L and low HDL cholestrol (0.83) mmol/L. LAL enzyme showed low levels of 13 pmol/hour (normal 80–230) in dried blood spots. Liver biopsy showed severe microvesicular steatosis and bridging fibrosis. She has c.684delT and c.894G>A pathogenic mutations. The child with LAL-D has received Sebelipase Alfa Kanuma®, intravenous therapy every two weeks at 1 mg/kg. She has tolerated the infusions well for the last twelve months with no adverse effects. The liver enzymes and lipid profile have normalized. Liver stiffness measured by transient elastography at baseline was 8.6kPa; after10 months of therapy liver stiffness improved to 7.4 kPa. Enzyme replacement therapy for LAL-D appears to be safe and preliminary results are encouraging. The therapy was started after significant advocacy from the family as the drug is not yet approved for coverage in Canada. Improvement in ALT and AST None
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.004 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.009 | 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".