{"id":"1d871e23-dc65-575d-9c0f-814376cad05b","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-clin-zip8-respiratory-chain","predicate":"was_associated_with","statement":"Patient 1 had low liver complex IV and II+III activities, elevated complex I, borderline-low muscle complex IV and reduced pyruvate dehydrogenase activity.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f49478e2-cdff-5853-9448-27cce7b75d78","mechanism_event_label":"The affected child had several mitochondrial enzyme abnormalities, without proof that each enzyme directly requires manganese.","subject":{"id":"fa612614-e2e4-5c16-b6a3-690c2d78effe","slug":"human-slc39a8-deficiency","display_name":"Human SLC39A8 transport deficiency","entity_type_key":"cellular_process"},"object":{"id":"9fce25b8-defb-506b-a4d2-eb81d2d5862e","slug":"mitochondrial-respiratory-enzyme-activity","display_name":"Mitochondrial respiratory enzyme activities","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f49478e2-cdff-5853-9448-27cce7b75d78","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-clin-zip8-respiratory-chain-event","event_type":"observed_intervention","label":"The affected child had several mitochondrial enzyme abnormalities, without proof that each enzyme directly requires manganese.","description":"Patient 1 had low liver complex IV and II+III activities, elevated complex I, borderline-low muscle complex IV and reduced pyruvate dehydrogenase activity.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"059eea33-6e24-58ca-970f-014e2e65df77","slug":"slc39a8","display_name":"Human ZIP8 (SLC39A8)","entity_type_key":"protein"},"role":"affected_protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"fa612614-e2e4-5c16-b6a3-690c2d78effe","slug":"human-slc39a8-deficiency","display_name":"Human SLC39A8 transport deficiency","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9fce25b8-defb-506b-a4d2-eb81d2d5862e","slug":"mitochondrial-respiratory-enzyme-activity","display_name":"Mitochondrial respiratory enzyme activities","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"Human ZIP8 (SLC39A8) (affected_protein)","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/manganese-clinical-sources/riley2017.abstract.txt\", \"locator\": \"Indexed primary abstract\", \"file_sha256\": \"31e4e33ec5601d443fb2d469b2e2c7d1fd89c611db0f41938b43007952d0f005\", \"start_char\": 0, \"end_char\": 1732, \"text_sha256\": \"31e4e33ec5601d443fb2d469b2e2c7d1fd89c611db0f41938b43007952d0f005\", \"text_characters\": 1732}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Two sisters with homozygous SLC39A8 p.Cys113Ser","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Respiratory-chain tests in patient 1; manganese and transferrin measurements and galactose-plus-uridine response in patient 2.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Measurements were not performed in both sisters interchangeably. The proposed SOD2 explanation was not directly demonstrated; manganese had only recently been added and cannot explain the already observed 14-day galactose/uridine response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Manganese research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"manganese","display_name":"Manganese","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The affected child had several mitochondrial enzyme abnormalities, without proof that each enzyme directly requires manganese.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mn-clin-riley2017] A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders. (2017). https://pubmed.ncbi.nlm.nih.gov/27995398/ DOI: 10.1007/s10545-016-0010-6","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Patient-specific liver, muscle and blood measurements","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":"6e2ab00f-0796-56de-afda-5f9bb76ab592","evidence_kind":"source_excerpt","locator":"Lines 1216-1228","start_line":1216,"end_line":1228,"excerpt":"### mn-clin-zip8-respiratory-chain\nPatient 1 had low liver complex IV and II+III activities, elevated complex I, borderline-low muscle complex IV and reduced pyruvate dehydrogenase activity.\nCondition category: machinery_impairment\nnutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The affected child had several mitochondrial enzyme abnormalities, without proof that each enzyme directly requires manganese.\norganism: Homo sapiens\ntissue_or_cell_type: Patient-specific liver, muscle and blood measurements\nexperimental_model: Two sisters with homozygous SLC39A8 p.Cys113Ser\nlimitations: Measurements were not performed in both sisters interchangeably. The proposed SOD2 explanation was not directly demonstrated; manganese had only recently been added and cannot explain the already observed 14-day galactose/uridine response.\nexposure: Respiratory-chain tests in patient 1; manganese and transferrin measurements and galactose-plus-uridine response in patient 2.\ncross_nutrient: Human ZIP8 (SLC39A8) (affected_protein)\nevidence_span: {\"source_cache\": \"artifacts/manganese-clinical-sources/riley2017.abstract.txt\", \"locator\": \"Indexed primary abstract\", \"file_sha256\": \"31e4e33ec5601d443fb2d469b2e2c7d1fd89c611db0f41938b43007952d0f005\", \"start_char\": 0, \"end_char\": 1732, \"text_sha256\": \"31e4e33ec5601d443fb2d469b2e2c7d1fd89c611db0f41938b43007952d0f005\", \"text_characters\": 1732}\n[mn-clin-riley2017] A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders. (2017). https://pubmed.ncbi.nlm.nih.gov/27995398/ DOI: 10.1007/s10545-016-0010-6","model_system":"Two sisters with homozygous SLC39A8 p.Cys113Ser","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [mn-clin-riley2017] A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders. (2017). https://pubmed.ncbi.nlm.nih.gov/27995398/ DOI: 10.1007/s10545-016-0010-6","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"03224387-8a73-5b4f-906d-9f0be6625b7f","stable_key":"import-be889add-cec8-500b-be89-676431432a70","title":"Manganese: enzyme cofactors, glycosylation, transport 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":"f029ee5a1133a4f296047f06a6f0178deb9fd02e8d9707bc285bbe0f4e08fcb5","revision_id":"a77068c1-5a13-5aa9-bbac-d1cff6d34f15","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}