Novel biallelic GNE variants identified in a patient with chronic thrombocytopenia without any symptoms of myopathy.

Autor: Tsuda S; Center for Postgraduate Education and Training, National Center for Child Health and Development (NCCHD), 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan., Sakamoto A; Center for Postgraduate Education and Training, National Center for Child Health and Development (NCCHD), 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. sakamoto-a@ncchd.go.jp.; Division of Hematology, NCCHD, Tokyo, Japan. sakamoto-a@ncchd.go.jp., Kawaguchi H; Department of Pediatrics, National Defense Medical College, Saitama, Japan., Uchiyama T; Department of Human Genetics, NCCHD, Tokyo, Japan., Kaname T; Department of Genome Medicine, NCCHD, Tokyo, Japan., Yanagi K; Department of Genome Medicine, NCCHD, Tokyo, Japan., Kunishima S; Department of Medical Technology, School of Health Sciences, Gifu University of Medical Science, Gifu, Japan., Ishiguro A; Center for Postgraduate Education and Training, National Center for Child Health and Development (NCCHD), 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. ishiguro-a@ncchd.go.jp.; Division of Hematology, NCCHD, Tokyo, Japan. ishiguro-a@ncchd.go.jp.
Jazyk: angličtina
Zdroj: Annals of hematology [Ann Hematol] 2024 Nov 22. Date of Electronic Publication: 2024 Nov 22.
DOI: 10.1007/s00277-024-06104-0
Abstrakt: GNE encodes a rate-limiting enzyme that regulates the biosynthesis of a sialic acid precursor. As sialic acids are critical for the platelet membrane and muscle fibers, GNE variants cause GNE-related thrombocytopenia and GNE-related myopathy. Here, we report a neonate with thrombocytopenia that initially met the criteria for neonatal allo-immune thrombocytopenia (NAIT) but was resistant to treatments and then revealed novel biallelic heterozygous GNE variants without any symptoms of myopathy when diagnosed. NAIT was initially diagnosed due to alloantibodies against HPA5 and its mismatch between the patient and his mother. However, intravenous immunoglobulin therapy and platelet transfusions showed minimal improvement in the platelet count. Platelet counts remained around 60 × 10 9 /L, suggesting congenital thrombocytopenia. Gene panel sequencing at the age of 13 identified biallelic pathogenic variants of GNE. The patient did not exhibit any symptoms of muscular weakness, suggesting GNE-related myopathy. We demonstrated a GNE-related thrombocytopenia patient with novel biallelic heterozygous GNE variants. Clinical trials have involved the use of sialic acids or their precursors, as well as gene therapy, to treat GNE-related myopathy, which may slow or halt the progression of the disease. Therefore, early diagnosis of this disease may significantly impact its clinical course.
Competing Interests: Declarations. Compliance with ethical standards: This study was approved by the Ethics Committees of the NCCHD in May 2018 (#1818). Informed consent for this report was obtained from the patient and her parents. Competing interests: The authors declare no competing interests. Permission to reproduce material from other sources: In accordance with the regulations of the place where the article was accepted.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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