Abstract Number: PB1248
Meeting: ISTH 2022 Congress
Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » Platelet Function Disorders, Hereditary
Background: Hermansky-Pudlak syndrome (HPS) comprises eleven autosomal recessive multisystem disorders sharing bleeding diathesis and albinism, due to abnormalities in genes (HPS1 to HPS11) essential for lysosome-related organelles. Knowing the HPS subtype is important for prognosis and clinical management, since other relevant organ manifestations may be present depending on the affected gen
Aims: Assessing the platelet phenotype and genetic diagnosis in two siblings with mild bleeding symptoms and albinism
Methods: A 25yr old woman (IC) with oculocutaneous albinism, macular hypoplasia in both eyes, iris transillumination, long-life frequent epistaxis and irregular menses (ISTH-BAT=4), was enrolled in the Spanish Project of Inherited Platelet Disorders. Her sister has milder albinism and occasional epistaxis (ISTH-BAT=1). They showed no other clinically relevant features. We assessed full blood count, blood smears immunostaining of platelets proteins (P-IF), platelet aggregation, and glycoproteins (GPs) expression, agonist-induced P-selectin and CD63 secretion by flow cytometry, and whole mount electron microscopy (WMEM). DNAs were analyzed by HTS-gene panel and CNV, and candidate variants segregated by Sanger
Results: Patients showed normal platelet counts and volume. Platelet aggregation was impaired (20-25%) with arachidonic acid, TRAP and collagen, but normal with ADP and ristocetin. Platelets showed normal GPs levels (Ib/IX, IIb/IIIa, Ia, VI), mildly reduced (10-50%) P-selectin secretion and no CD63 release. P-IF in IC showed no CD63 staining, but normal CD62 or Lamp2 (Fig 1A). WMEM demonstrated a severe dense granule defect in both sisters. DNA analysis identified the heterozygous candidate variant c.632G>C [p.Gly211Ala] in HPS6 in the siblings, but not in their unaffected half-brother
Conclusion(s): Platelet phenotyping and HTS are valuable for diagnosis of patients with albinism. P-IF can be used to screen patients with albinism and mild bleeding symptoms; if CD63 staining is absent, HPS should be considered. The HPS6 missense variant c.632G>C [p.Gly211Ala] is rather frequent (MAF=0.0052), and has therefore a higher likelihood to occur homozygously
To cite this abstract in AMA style:
Palma-Barqueros V, Fernández-Mosteririn N, Zaninetti C, Pardiñas- Barón N, Zamora-Canovas A, Sánchez-Fuentes A, Revilla N, Rodríguez-Alen A, Marin-Quilez A, Díaz-Ajenjo L, Torrecillas A, Bohdan N, Padilla J, Miguel-García C, Vicente V, Lozano M, Greinacher A, Bastida J, Rivera J. Integrated diagnostic workflow in two siblings with albinism and suspected Hermansky-Pudlak syndrome [abstract]. https://abstracts.isth.org/abstract/integrated-diagnostic-workflow-in-two-siblings-with-albinism-and-suspected-hermansky-pudlak-syndrome/. Accessed March 22, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/integrated-diagnostic-workflow-in-two-siblings-with-albinism-and-suspected-hermansky-pudlak-syndrome/