Evaluation of the Sialidase Inhibitor Oseltamivir in GNE-associated Thrombocytopenia
(2021) The XXIX Congress of the International Society on Thrombosis and Haemostasis (ISTH) In Research and practice in thrombosis and haemostasis 5(S2). p.644-645- Abstract
- Background: GNE encodes UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the rate limiting enzyme of sialic acid biosynthesis. Biallelic variants in GNE have recently been associated with severe isolated macrothrombocytopenia, attributed to an increased clearance of desialylated platelets. Interestingly, treatment with the sialidase inhibitor oseltamivir has been reported to increase platelet counts in conditions such as immune thrombocytopenia (ITP) and influenza. We present a case of a 17-year-old boy (the proband) with severe congenital macrothrombocytopenia (platelet counts < 10 x 109/L). Whole genome sequencing revealed two previously undescribed compound heterozygous variants in GNE (c.416_426del, p.Ile139Argfs*4... (More)
- Background: GNE encodes UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the rate limiting enzyme of sialic acid biosynthesis. Biallelic variants in GNE have recently been associated with severe isolated macrothrombocytopenia, attributed to an increased clearance of desialylated platelets. Interestingly, treatment with the sialidase inhibitor oseltamivir has been reported to increase platelet counts in conditions such as immune thrombocytopenia (ITP) and influenza. We present a case of a 17-year-old boy (the proband) with severe congenital macrothrombocytopenia (platelet counts < 10 x 109/L). Whole genome sequencing revealed two previously undescribed compound heterozygous variants in GNE (c.416_426del, p.Ile139Argfs*4 and c.1352G>A, p.Arg451Gln). The proband was otherwise healthy, with no signs of GNE myopathy.
Aims: To investigate the consequences of the identified variants in GNE and evaluate the effect of oseltamivir in GNE-associated thrombocytopenia.
Methods: Sialylation of platelets, granulocytes, lymphocytes and monocytes was determined by flow cytometry in the proband and healthy controls (n = 5), using Sambucus nigra lectin (SNA) and Maackia amurensis lectin II (MAL II). Platelet sialylation was reassessed in the proband following treatment with oseltamivir (75 mg twice daily, off-label use). Informed consent was obtained from all participants. The study was approved by the regional ethical committee.
Results: Sialylation of platelets and leukocytes was markedly decreased in the proband compared with the healthy controls, consistent with a deleterious effect of the compound heterozygous variants in GNE (Figure 1). Platelet sialylation was persistently decreased after 18 days of treatment with oseltamivir, and no clinically significant elevation of the platelet counts could be observed (Figure 1, Figure 2). (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/58968d01-3136-4b53-96ab-a22e4c754226
- author
- Fager Ferrari, Marcus
LU
; Smolag Klosowska, Karolina LU
; Zetterberg, Eva LU ; Leinoe, Eva ; Blom, A.M. ; Ek, Torben ; Rossing, Maria and Martin, Myriam LU
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Research and practice in thrombosis and haemostasis
- volume
- 5
- issue
- S2
- article number
- PB0871
- pages
- 644 - 645
- publisher
- Wiley
- conference name
- The XXIX Congress of the International Society on Thrombosis and Haemostasis (ISTH)
- conference dates
- 2021-07-17 - 2021-07-21
- ISSN
- 2475-0379
- language
- English
- LU publication?
- yes
- id
- 58968d01-3136-4b53-96ab-a22e4c754226
- alternative location
- https://abstracts.isth.org/abstract/evaluation-of-the-sialidase-inhibitor-oseltamivir-in-gne-associated-thrombocytopenia
- date added to LUP
- 2021-10-10 12:31:57
- date last changed
- 2021-10-26 07:40:38
@misc{58968d01-3136-4b53-96ab-a22e4c754226, abstract = {{Background: GNE encodes UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the rate limiting enzyme of sialic acid biosynthesis. Biallelic variants in GNE have recently been associated with severe isolated macrothrombocytopenia, attributed to an increased clearance of desialylated platelets. Interestingly, treatment with the sialidase inhibitor oseltamivir has been reported to increase platelet counts in conditions such as immune thrombocytopenia (ITP) and influenza. We present a case of a 17-year-old boy (the proband) with severe congenital macrothrombocytopenia (platelet counts < 10 x 109/L). Whole genome sequencing revealed two previously undescribed compound heterozygous variants in GNE (c.416_426del, p.Ile139Argfs*4 and c.1352G>A, p.Arg451Gln). The proband was otherwise healthy, with no signs of GNE myopathy. <br> <br> Aims: To investigate the consequences of the identified variants in GNE and evaluate the effect of oseltamivir in GNE-associated thrombocytopenia.<br> <br> Methods: Sialylation of platelets, granulocytes, lymphocytes and monocytes was determined by flow cytometry in the proband and healthy controls (n = 5), using Sambucus nigra lectin (SNA) and Maackia amurensis lectin II (MAL II). Platelet sialylation was reassessed in the proband following treatment with oseltamivir (75 mg twice daily, off-label use). Informed consent was obtained from all participants. The study was approved by the regional ethical committee.<br> <br> Results: Sialylation of platelets and leukocytes was markedly decreased in the proband compared with the healthy controls, consistent with a deleterious effect of the compound heterozygous variants in GNE (Figure 1). Platelet sialylation was persistently decreased after 18 days of treatment with oseltamivir, and no clinically significant elevation of the platelet counts could be observed (Figure 1, Figure 2).}}, author = {{Fager Ferrari, Marcus and Smolag Klosowska, Karolina and Zetterberg, Eva and Leinoe, Eva and Blom, A.M. and Ek, Torben and Rossing, Maria and Martin, Myriam}}, issn = {{2475-0379}}, language = {{eng}}, note = {{Conference Abstract}}, number = {{S2}}, pages = {{644--645}}, publisher = {{Wiley}}, series = {{Research and practice in thrombosis and haemostasis}}, title = {{Evaluation of the Sialidase Inhibitor Oseltamivir in <i>GNE</i>-associated Thrombocytopenia}}, url = {{https://abstracts.isth.org/abstract/evaluation-of-the-sialidase-inhibitor-oseltamivir-in-gne-associated-thrombocytopenia}}, volume = {{5}}, year = {{2021}}, }