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Diabetic Kidney Disease — UKMLA MCQ

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HardEndocrinologyDiabetic Kidney DiseaseUKMLAMRCGP AKTPARAMRCP Part 1PSA

Several members of three generations have delayed bleeding 12–24 hours after dental extraction or surgery, mild thrombocytopenia and poor wound healing. PT, APTT and plasma fibrinolysis tests are normal, but platelet alpha-granule proteins are extensively degraded and platelet urokinase-type plasminogen activator is increased more than 100-fold. Which molecular lesion is most likely?

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Correct answer: E — Heterozygous tandem duplication involving PLAU

The best answer is “Heterozygous tandem duplication involving PLAU”. Quebec platelet disorder is an autosomal dominant, platelet-dependent gain-of-function defect in fibrinolysis caused by a tandem duplication containing PLAU. Enhancer rewiring drives marked megakaryocyte-specific urokinase overexpression; intraplatelet plasmin then degrades alpha-granule proteins, and released urokinase accelerates lysis locally after platelet activation. Plasma fibrinolysis can therefore appear normal despite delayed challenge-related bleeding. SERPINF2 and SERPINE1 deficiencies cause systemic primary hyperfibrinolysis, factor-XIII deficiency causes unstable fibrin without platelet urokinase excess, and ANO6 deficiency impairs procoagulant phosphatidylserine exposure.

Reference: Enhancer-gene rewiring in the pathogenesis of Quebec platelet disorder: https://pmc.ncbi.nlm.nih.gov/articles/PMC7735161/