{"id":"7627d869-0fdd-5ded-8218-0e8fbe88f9bb","stable_key":"3b5aff9b-4086-5574-bfb4-3ea49ba520d7:coq10-etfdh-coq-low","predicate":"variants_associated_with_low","statement":"All seven patients in the 2007 ETFDH-associated myopathy series had significantly reduced muscle CoQ10.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ff7a6c24-3707-52cf-bd59-4e0b8a4b5630","mechanism_event_label":"A defect outside the core COQ synthesis genes accompanied low muscle CoQ in this group.","subject":{"id":"9f78394a-ddd1-5874-a9f7-e848262b5761","slug":"etfdh","display_name":"Human electron transfer flavoprotein dehydrogenase / ETFDH","entity_type_key":"protein"},"object":{"id":"9c185815-74b8-5542-b236-f302b620c1e8","slug":"coq-muscle-concentration","display_name":"Muscle coenzyme Q10 concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ff7a6c24-3707-52cf-bd59-4e0b8a4b5630","stable_key":"3b5aff9b-4086-5574-bfb4-3ea49ba520d7:coq10-etfdh-coq-low-event","event_type":"observed_intervention","label":"A defect outside the core COQ synthesis genes accompanied low muscle CoQ in this group.","description":"All seven patients in the 2007 ETFDH-associated myopathy series had significantly reduced muscle CoQ10.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9f78394a-ddd1-5874-a9f7-e848262b5761","slug":"etfdh","display_name":"Human electron transfer flavoprotein dehydrogenase / ETFDH","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9c185815-74b8-5542-b236-f302b620c1e8","slug":"coq-muscle-concentration","display_name":"Muscle coenzyme Q10 concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/coq10-research/17412732.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"38627f0140b8d1f861ce0e836bc8ac1edc9684314e8d664f3040e1c3fff42494\", \"start_char\": 0, \"end_char\": 1533, \"text_sha256\": \"38627f0140b8d1f861ce0e836bc8ac1edc9684314e8d664f3040e1c3fff42494\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Genetic case series and muscle biochemistry","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Biallelic ETFDH variants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Secondary CoQ depletion reported in this cohort; later cohorts did not reproduce universal muscle depletion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"coq10","display_name":"Coenzyme Q10 / CoQ10 redox system","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Seven patients from five families","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A defect outside the core COQ synthesis genes accompanied low muscle CoQ in this group.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[coq10-p17412732] The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. (2007). https://pubmed.ncbi.nlm.nih.gov/17412732/ DOI: 10.1093/brain/awm054","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"ETFDH-associated myopathy","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"0df68fdb-a3ea-5093-b4cd-26ffe8ec8b15","evidence_kind":"source_excerpt","locator":"Lines 1061-1072","start_line":1061,"end_line":1072,"excerpt":"### coq10-etfdh-coq-low\nAll seven patients in the 2007 ETFDH-associated myopathy series had significantly reduced muscle CoQ10.\nCondition category: machinery_impairment\nnutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A defect outside the core COQ synthesis genes accompanied low muscle CoQ in this group.\norganism: Seven patients from five families\ntissue_or_cell_type: ETFDH-associated myopathy\nexperimental_model: Genetic case series and muscle biochemistry\nlimitations: Secondary CoQ depletion reported in this cohort; later cohorts did not reproduce universal muscle depletion.\nexposure: Biallelic ETFDH variants\nevidence_span: {\"source_cache\": \"artifacts/coq10-research/17412732.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"38627f0140b8d1f861ce0e836bc8ac1edc9684314e8d664f3040e1c3fff42494\", \"start_char\": 0, \"end_char\": 1533, \"text_sha256\": \"38627f0140b8d1f861ce0e836bc8ac1edc9684314e8d664f3040e1c3fff42494\"}\n[coq10-p17412732] The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. (2007). https://pubmed.ncbi.nlm.nih.gov/17412732/ DOI: 10.1093/brain/awm054","model_system":"Genetic case series and muscle biochemistry","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [coq10-p17412732] The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. (2007). https://pubmed.ncbi.nlm.nih.gov/17412732/ DOI: 10.1093/brain/awm054","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"fc6c2f3b-14a3-59de-848e-ca1c02fee1df","stable_key":"import-3b5aff9b-4086-5574-bfb4-3ea49ba520d7","title":"Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"053f9a6f6c17321fa9fd271486d7f20a86a49b237424108de7dc8663372e73bf","revision_id":"028900ce-8ca4-5d13-8c86-6e327c071e64","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"677274c2-0e35-5922-ba79-f9b881f10399","title":"ETFDH-related myopathy: depleted muscle CoQ versus no deficit after mitochondrial normalization","kind":"contradiction","status":"open","why":"The 2007 series reported low muscle CoQ in every patient; the 2013 study explicitly revisited that conclusion and found an elevated bulk pool with no deficit after citrate-synthase normalization. This challenges a universal secondary-CoQ-deficiency interpretation of ETFDH disease.","resolution":"Keep each cohort and assay denominator. Genotype, riboflavin responsiveness, mitochondrial proliferation and normalization are candidate contributors; none establishes that every ETFDH defect either depletes or preserves CoQ. Measure the affected tissue rather than infer status from the gene alone.","created_at":"2026-09-17 21:53:19","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/677274c2-0e35-5922-ba79-f9b881f10399","sides":[{"conflict_id":"677274c2-0e35-5922-ba79-f9b881f10399","ordinal":0,"label":"A defect outside the core COQ synthesis genes accompanied low muscle CoQ in this group.","revision_id":"028900ce-8ca4-5d13-8c86-6e327c071e64","start_line":1061,"end_line":1072,"quote":"### coq10-etfdh-coq-low\nAll seven patients in the 2007 ETFDH-associated myopathy series had significantly reduced muscle CoQ10.\nCondition category: machinery_impairment\nnutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A defect outside the core COQ synthesis genes accompanied low muscle CoQ in this group.\norganism: Seven patients from five families\ntissue_or_cell_type: ETFDH-associated myopathy\nexperimental_model: Genetic case series and muscle biochemistry\nlimitations: Secondary CoQ depletion reported in this cohort; later cohorts did not reproduce universal muscle depletion.\nexposure: Biallelic ETFDH variants\nevidence_span: {\"source_cache\": \"artifacts/coq10-research/17412732.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"38627f0140b8d1f861ce0e836bc8ac1edc9684314e8d664f3040e1c3fff42494\", \"start_char\": 0, \"end_char\": 1533, \"text_sha256\": \"38627f0140b8d1f861ce0e836bc8ac1edc9684314e8d664f3040e1c3fff42494\"}\n[coq10-p17412732] The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. (2007). https://pubmed.ncbi.nlm.nih.gov/17412732/ DOI: 10.1093/brain/awm054","source_key":"import-3b5aff9b-4086-5574-bfb4-3ea49ba520d7","source_title":"Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17)","claim_ids":["7627d869-0fdd-5ded-8218-0e8fbe88f9bb"]},{"conflict_id":"677274c2-0e35-5922-ba79-f9b881f10399","ordinal":1,"label":"More mitochondria can change a bulk tissue measurement without increasing CoQ per mitochondrial mass.","revision_id":"028900ce-8ca4-5d13-8c86-6e327c071e64","start_line":1074,"end_line":1085,"quote":"### coq10-etfdh-coq-normalized\nMuscle CoQ was elevated in the 34-patient cohort but not significantly different from controls after normalization to citrate synthase.\nCondition category: machinery_impairment\nnutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: More mitochondria can change a bulk tissue measurement without increasing CoQ per mitochondrial mass.\norganism: 34 riboflavin-responsive ETFDH-MADD patients\ntissue_or_cell_type: Muscle CoQ and mitochondrial mass\nexperimental_model: Muscle HPLC, citrate-synthase normalization and mtDNA measurements\nlimitations: Different variants/cohort from the earlier report; bulk concentration and concentration per mitochondrial mass are different measurements.\nexposure: Genetically defined MADD cohort\nevidence_span: {\"source_cache\": \"artifacts/coq10-research/23628458.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"4395652f36b9a39c5de72db7abb11b7f42b7e3124b1dfd3c8cd2a0212a9f7de6\", \"start_char\": 0, \"end_char\": 1706, \"text_sha256\": \"4395652f36b9a39c5de72db7abb11b7f42b7e3124b1dfd3c8cd2a0212a9f7de6\"}\n[coq10-p23628458] Increased muscle coenzyme Q10 in riboflavin responsive MADD with ETFDH gene mutations due to secondary mitochondrial proliferation. (2013). https://pubmed.ncbi.nlm.nih.gov/23628458/ DOI: 10.1016/j.ymgme.2013.04.007","source_key":"import-3b5aff9b-4086-5574-bfb4-3ea49ba520d7","source_title":"Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17)","claim_ids":["da96de83-4c94-58b8-af1e-f30ef5113cfe"]}]}],"corrections":[],"research":null}