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Adult type I Gaucher disease with splenectomy caused by a compound heterozygous GBA1 mutation in a Chinese patient: a case report

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Abstract

Gaucher disease (GD) is an autosomal recessive ailment resulting from glucocerebrosidase deficiency caused by a mutation in the GBA1 gene, leading to multi-organ problems in the liver, spleen, and bone marrow. In China, GD is extremely uncommon and has a lower incidence rate than worldwide. In this study, we report the case of an adult male with an enlarged spleen for 13 years who presented with abdominal distension, severe loss of appetite and weight, reduction of the three-line due to hypersplenism, frequent nosebleeds, and bloody stools. Regrettably, the unexpected discovery of splenic pathology suggestive of splenic Gaucher disease was only made after a splenectomy due to a lack of knowledge about rare disorders. Our patient's delayed diagnosis may have been due to the department where he was originally treated, but it highlights the need for multidisciplinary consultation in splenomegaly of unknown etiology. We then investigated the patient's clinical phenotypes and gene mutation features using genetically phenotypical analysis. The analysis of the GBA1 gene sequence indicated that the patient carried a compound heterozygous mutation consisting of two potentially disease-causing mutations: c.907C > A (p. Leu303Ile) and c.1448 T > C (p. Leu483Pro). While previous research has linked the p. Leu483Pro mutation site to neurologic GD phenotypes (GD2 and GD3), the patients in this investigation were identified as having non-neuronopathic GD1. The other mutation, p. Leu303Ile, is a new GD-related mutation not indexed in PubMed that enriches the GBA1 gene mutation spectrum. Biosignature analysis has shown that both mutations alter the protein's three-dimensional structure, which may be a pathogenic mechanism for GD1 in this patient.

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Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author upon reasonable request.

Abbreviations

GD:

Gaucher disease

HLD-C:

High-density lipoprotein cholesterol

ApoA:

Apolipoprotein A

NGS:

Next-generation sequencing

ERT:

Enzyme replacement therapy

HGMD:

Human Gene Mutation Database

GWAS:

Genome-wide association studies

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Funding

This work was supported by the Fujian Province Medical Innovation Foundation (2022CXB002, 2022CXA001, 2021CXB001), the Fujian Province Natural Science Fund Project (2022J01409, 2021J02053, 2023J011159, 2022J01996), the Special Research Foundation of Fujian Provincial Department of Finance (No. 2023–830, 2021–848, 2021–917, 2022–840), and National famous and old Chinese medicine experts (Xuemei Zhang, Xiaohua Yan) inheritance studio construction project.

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Author notes

  1. Jian-hui Zhang, Hui Chen, Dan-dan Ruan, Ying Chen and Li Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Traditional Chinese Medicine, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, No.134 Dong Street, Fuzhou, 350001, China

    Jian-hui Zhang, Hui Chen, Dan-dan Ruan, Ying Chen, Li Zhang, Mei-zhu Gao, Qian Chen, Hong-ping Yu, Jia-yi Wu, Xin-fu Lin, Zhu-ting Fang, Xiao-ling Zheng, Jie-wei Luo, Li-sheng Liao & Hong Li

  2. Department of Traditional Chinese Medicine, Fujian Provincial Hospital, Fuzhou, China

    Ying Chen, Jie-wei Luo & Hong Li

  3. Department of Nephrology, Fujian Provincial Hospital, Fuzhou, China

    Li Zhang & Mei-zhu Gao

  4. Department of Pediatrics, Fujian Provincial Hospital, Fuzhou, China

    Xin-fu Lin

  5. Department of Digestive Endoscopy, Fujian Provincial Hospital, Fuzhou, China

    Xiao-ling Zheng

  6. Department of Hematology, Fujian Provincial Hospital, Fuzhou, China

    Li-sheng Liao

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  1. Jian-hui Zhang
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Contributions

Data collection: JHZ, MZG, QC and HPY. Data analysis, and drafting of the article: JHZ, HC, DDR, YC and LZ. Provision of table and figures: JYW, XFL and ZTF. Design, supervision, and editing of the manuscript: LSL, XLZ, HL and JWL. All the authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Xiao-ling Zheng, Jie-wei Luo, Li-sheng Liao or Hong Li.

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All procedures were performed in accordance to the tenets of the Declaration of Helsinki and the study was approved by the Ethics Committee of Fujian Provincial Hospital, Fuzhou, China. All participants and legal guardians of the minors involved in the present study provided written informed consent.

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Written informed consent for publication this study was obtained from the patients and their guardians. A copy of those written consents is available for review by the Editor-in-Chief of this journal.

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Zhang, Jh., Chen, H., Ruan, Dd. et al. Adult type I Gaucher disease with splenectomy caused by a compound heterozygous GBA1 mutation in a Chinese patient: a case report. Ann Hematol 103, 1765–1774 (2024). https://doi.org/10.1007/s00277-024-05710-2

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