Glycogenosis type XI, a rare association between muscle and skin manifestations - the contribution of proteomics for the understanding of the underlying myopathology
Bibliographic record
Abstract
Background: Glycogenosis type 11 or deficiency in lactate dehydrogenase A (LDHA) (OMIM: 612933) is an ultra-rare condition of perturbed glycogen metabolism, first described in 1980 in a Japanese patient, and quite rare outside Japan. There are very few cases described in the literature and there is limited awareness of this condition that can easily be misdiagnosed or remain undiagnosed. Objective: To report on an ultra-rare form of glycogenosis stressing the association with cutaneous features and raise awareness for this rare condition. We report a novel pathogenic variant and aim to contribute to the understanding of the myopathophysiological mechanisms of disease by proteomics. Methods: We report the clinical, histopathological, magnetic resonance, genetic and proteomic features of a 19-year-old male of North African background that presented from infancy episodes of muscle pain, contractures and high CK levels immediately after moderate to high-intensity exercise. The patient was followed for several years prior to our observation due to severe acne that involved mostly the back and was resistant to treatment. Results: The phenotype of this patient is similar to the ones previously described with muscle and skin involvement. The MRI functional studies, interrupted at 2’30’’ due to muscle pain, allowed us to confirm the presence of a metabolic disturbance of the muscles. The histological features of the muscle were quite subtle consisting mainly in rare subsarcolemmal vacuoles also identified at ultra-structural level. Immunostaining with the antibody targeting LDHA showed intracytoplasmic aggregates of the protein unlike the normal control that presented a diffuse staining. Exome analysis revealed a novel bi-allelic frameshifting deletion in exon 7 of the LDHA gene; c.766_767delGT. Proteomic findings accord with loss of functional LDHA and provide significant insights into the pathobiochemistry of the disease. Conclusions: Our combined data expand the current genetic landscape of LDHA-related disease, confirms the concept of a metabolic-driven vacuolar myopathy and provides insights into the biochemical nature of myopathology.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".