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Myopathy, Lactic Acidosis, and Sideroblastic Anemia

Myopathy, Lactic Acidosis, and Sideroblastic Anemia Deep Research Fallback

⚠️ Fallback MONDO:0000863

Myopathy, Lactic Acidosis, and Sideroblastic Anemia Deep Research Fallback

Provider Attempts

  • 2026-05-07: timeout 90s just research-disorder falcon Myopathy_Lactic_Acidosis_and_Sideroblastic_Anemia timed out with exit code 124 after the provider command was terminated by timeout.
  • 2026-05-07: timeout 90s just research-disorder openai Myopathy_Lactic_Acidosis_and_Sideroblastic_Anemia timed out with exit code 124 after the provider command was terminated by timeout.

No provider-generated deep-research artifact was available to integrate. Curation therefore proceeded from generated structured Orphanet evidence and fetched PubMed caches, without hand-editing any references_cache/*.md files.

Evidence Scope Used For Curation

  • ORPHA:2598 structured record for disease definition, MONDO and OMIM cross references, autosomal recessive inheritance, point prevalence, PUS1 and YARS2 gene associations, and HPO phenotype rows.
  • PMID:15108122 for the original PUS1-associated MLASA families and the framing of MLASA as an autosomal recessive oxidative phosphorylation disorder affecting skeletal muscle and bone marrow.
  • PMID:15772074 for absent or reduced PUS1-dependent mitochondrial tRNA pseudouridylation as a molecular pathogenesis mechanism.
  • PMID:17056637 for PUS1 loss-of-function evidence, reduced mitochondrial translation, and combined respiratory-chain defects.
  • PMID:20598274 for YARS2 as a cause of MLASA and the mechanism linking reduced mitochondrial tRNA aminoacylation to impaired mitochondrial protein synthesis and respiratory-chain dysfunction.
  • PMID:23918765 for YARS2/PUS1 sequencing as a diagnostic strategy, severe myopathy with respiratory failure requiring ventilatory support, and supportive clinical management.
  • PMID:25037980 for MT-ATP6-associated MLASA plus syndrome, including complex V dysfunction and impaired oligomycin-sensitive respiration.
  • PMID:28395030 for the broader YARS2 clinical cohort, elevated lactate, generalized myopathy, sideroblastic anemia, COX deficiency, and surveillance recommendations.
  • PMID:30026338 for the YARS2 phenotypic spectrum, YARS2 enzymatic function, ringed sideroblast pathology, ragged-red fiber myopathy, and pyridoxine treatment nonresponse.

Curation Conclusions

The curated graph models MLASA as genetically heterogeneous mitochondrial disease involving PUS1, YARS2, and MT-ATP6. PUS1 deficiency disrupts mitochondrial tRNA pseudouridylation, YARS2 deficiency disrupts mitochondrial tyrosyl-tRNA aminoacylation, and MT-ATP6 variation impairs ATP synthase complex V. These upstream defects converge on impaired mitochondrial translation and respiratory-chain dysfunction, supporting the clinical triad of mitochondrial myopathy, lactic acidosis, and sideroblastic anemia. The entry also records ORPHA-supported dysmorphic, skeletal, neurologic, endocrine, ocular, cardiorespiratory, biochemical, diagnostic, histopathologic, and supportive management features where exact cached snippets support them.