PB0691 - Kabuki syndrome complicated by severe immune thrombocytopenia and autoimmune thyroiditis: identification of a novel pathogenic mutation

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Xinmiao Qu

Tianjin
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Tianjin, Tianjin, China (People's Republic)

Co-Author(s)

Feng Xue, MD

Chief physician
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin 300020, China
Tianjin, Tianjin, China (People's Republic)
WL

Wei Liu

professor
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases
tianjin, Tianjin, China (People's Republic)
YC

Yunfei Chen

Tianjin
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases
Tianjin, Tianjin, China (People's Republic)
Renchi Yang, MD

Head of Thrombosis and Hemostasis Center
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Tianjin, Hebei, China (People's Republic)
XL

Xiaofan Liu

Tianjin
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases
Tianjin, Tianjin, China (People's Republic)
LZ

Lei Zhang

professor
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin 300020, China
Tianjin, Tianjin, China (People's Republic)
RF

Rongfeng Fu

Tianjin
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases
Tianjin, Tianjin, China (People's Republic)

Background: Kabuki syndrome (KS) constitutes a rare congenital disorder characterized by multiple systemic abnormalities and predominantly stems from pathogenic mutations in the KMT2D or KDM6A genes. Truncating-type mutations in KMT2D which lead to the loss of the SET domain always result in more severe and characteristic manifestation. The concurrent presentation of KS, immune thrombocytopenia (ITP), and autoimmune thyroiditis (AIT) has been scarcely reported in the literature. Although treatment of KS is focused on symptomatic combination therapy, the immune dysregulation inherent to KS poses challenges in addressing complications.

Aims: We aimed to elucidate a new KMT2D mutation and provide basis for facilitating treatment.

Methods: This report detailed a distinct case involving a 9-year-old KS patient with concomitant severe ITP and AIT in the absence of any familial history. Genomic DNA was extracted from the patient’s peripheral blood and investigated using Whole-exome sequencing (WES). The conformational changes of KMT2D protein were predicted using SWISS-MODEL (Figure 1). PCR targeted amplification and Sanger sequencing were performed to confirm the mutation and familial pedigree in the candidate gene.

Results: The patient presents with specific facial features, neurodevelopmental dysfunction, skeletal and organ anomalies, developmental delay and liver abnormalities. A novel genetic aberration was identified in this patient: a previously unreported truncating-type mutation in KMT2D (c.8796_8797delGA, p.Lys2933Thrfs*8), leading to the loss of the crucial SET domain in the KMT2D protein, exacerbating the hallmark clinical features of KS. To manage ITP relapse, a therapeutic regimen incorporating methylprednisolone and recombinant human thrombopoietin (rhTPO), selected for its minimal hepatic impact, was administered, yielding a sustained improvement in platelet count.

Conclusion(s): This report not only broadens our understanding of the genetic landscape for KS but also underscores the therapeutic potential of rhTPO in managing KS with ITP, especially in patients with liver abnormalities.