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IEMbase 0746: CYCS-related mitochondrial cytochrome c deficiency

Scope

Field Value
IEMbase ID 746
Nosology 8.3.03.01
Nosology code IEM0489
Gene CYCS
External IDs OMIM:612004; ORPHA:168629
Generated mapping UNMAPPED; weak candidate Mitochondrial_Trifunctional_Protein_Deficiency.yaml
Candidate DisMech targets CYCS-Related_Thrombocytopenia.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase labels this record CYCS-related mitochondrial cytochrome c deficiency, with alternate name thrombocytopenia type 4. It is autosomal dominant. The cached rows are highly specific and hematologic: decreased blood thrombocytes from childhood through adulthood and characteristic thrombocytopenia across the same age bands.

DisMech phenotype coverage

CYCS-Related_Thrombocytopenia.yaml is the exact local target despite the generated mapper miss. The DisMech entry deliberately models the OMIM:612004 / ORPHA:168629 disease identity as CYCS-related thrombocytopenia 4 rather than as a generic cytochrome c oxidase deficiency. It captures autosomal dominant CYCS missense variants, altered cytochrome c respiratory and apoptotic function, dysregulated megakaryocyte platelet release, and isolated mild-to-moderate thrombocytopenia with normal platelet size.

The generated Mitochondrial_Trifunctional_Protein_Deficiency.yaml candidate is a false positive with no disease-identity relationship to CYCS thrombocytopenia.

Concordance and completeness

Judgement: false negative; resolve to exact CYCS-Related_Thrombocytopenia.yaml.

IEMbase is concise but concordant for the dominant clinical phenotype: low platelets/thrombocytopenia. DisMech is more complete mechanistically and nosologically, especially in clarifying that CYCS is mitochondrial but the curated disease entity is thrombocytopenia 4 rather than a syndromic COX assembly disorder.

Curation actions

  • Treat CYCS-Related_Thrombocytopenia.yaml as the exact local mapping.
  • Reject Mitochondrial_Trifunctional_Protein_Deficiency.yaml as exact coverage.
  • Preserve the IEMbase label caveat: primary label says mitochondrial cytochrome c deficiency, while the disease identity is thrombocytopenia type 4 / CYCS-related thrombocytopenia.