Congenital-onset MLASA2 from a novel <i>YARS2</i> variant: A literature review
Bibliographic record
Abstract
Introduction MLASA (myopathy, lactic acidosis and sideroblastic anemia) is a rare, autosomal recessive mitochondrial disorder. Symptom onset typically occurs in childhood and differs considerably in disease severity. Congenital-onset disease is uncommon. Methods Whole genome sequencing was performed which identified two heterozygous, rare YARS2 (NM_001040436.3) variants in trans , one of which was novel. The diagnosis was confirmed with muscle biopsy and mitochondrial enzyme activity testing. To compare the clinical phenotype of our patient to those previously described in the literature, we reviewed all YARS2 -related cases in literature to identify age of symptom onset and associated clinical features. Results The maternally-inherited variant, c.948G > T, p.(Arg316Ser), was previously reported with MLASA; the paternally-inherited variant, c.917T > C, p.(Phe306Ser) has not been previously reported. Muscle biopsy showed non-specific changes, that can be seen with mitochondrial dysfunction. Mitochondrial enzyme activity testing on frozen muscle tissue confirmed reduced complex I, III and IV activities. Discussion In our case report we describe a patient with MLASA, caused by compound heterozygous variants in YARS2 . Our child with congenital-onset disease remains stable at 23 months old. Her stable course differs from two other children with congenital-onset disease who died in the first few days to months after birth. Mitochondrial enzyme activity testing is important to establish pathogenicity of novel variants in patients with this rare and clinically heterogeneous disease.
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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 | 0.001 |
| 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".