Journal Article

Macrothrombocytopenia with leukocyte inclusions in a patient with Wilson disease: a case report and literature review

Cai, Jianling, Yu, Meidie, Lin, Shaoze, Chen, Hongxing, Huang, Zhanqin, Zhang, Dongqing, Huang, Yuxuan

2024

Overview

Background Wilson disease (WD) is an autosomal recessive disorder caused by homozygous or compound heterozygous mutations in ATP7B . Clinical manifestations primarily involve liver and nervous system lesions, with rarely observed hematologic manifestations. Case presentation In the present case, a patient with WD presented with thrombocytopenia, giant platelets, and Döhle-like cytoplasmic inclusions in the leukocytes. Initially, the May–Hegglin anomaly was considered; however, whole-exome sequencing did not reveal any mutation in the MYH9 gene but a heterozygous mutation was found in (C.2804 C > T, p.T935M) in the ATP7B gene. After two years, the patient developed tremors in his hands, lower limb stiffness, and foreign body sensation in the eyes. Additionally, Kayser–Fleischer rings in the corneal limbus were detected by slit-lamp examination. Copper metabolism test indicated a slight decrease in serum ceruloplasmin. Transmission electron microscopy revealed that the inclusion bodies of leukocytes were swollen mitochondria. Mass spectrometry analysis showed that the copper levels were almost 20-fold higher in the leukocytes of the patient than in those of the control group. Based on the Leipzig scoring system, a diagnosis of WD was confirmed. Zinc sulfate treatment ameliorated the patient’s symptoms and enhanced platelet, serum ceruloplasmin, and albumin levels. Conclusions In conclusion, this case represents the first documented instance of WD presenting as thrombocytopenia, giant platelets, and Döhle-like cytoplasmic inclusions in the leukocytes. Excessive cellular copper accumulation likely underlies these findings; however, understanding precise mechanisms warrants further investigation.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Albumin / Anemia / Asymptomatic / ATP7B gene / Biomedical and Life Sciences / Biomedicine / Blood / Blood platelets / Bone marrow / Care and treatment / Case Report / Ceruloplasmin / Copper / Copper-Transporting ATPases - genetics / Copper-Transporting ATPases - metabolism / Cornea / Diagnosis / Diseases / Foreign bodies / Gene Expression / Gene mutations / Genetic aspects / Giant platelets / Health aspects / Hematology / Hepatolenticular Degeneration - complications / Hepatolenticular Degeneration - genetics / Hepatolenticular Degeneration - pathology / Hereditary diseases / Heterozygote / Hospital patients / Human Genetics / Humans / Inclusion bodies / Inclusion Bodies - metabolism / Inclusion Bodies - pathology / Leukocyte inclusions / Leukocytes / Leukocytes - metabolism / Leukocytes - pathology / Literature reviews / Liver / Liver cirrhosis / Liver diseases / Magnetic resonance imaging / Male / Mass spectrometry / Mass spectroscopy / Medical treatment / Metabolism / Microarrays / Mitochondria / Mutation / MYH9 gene / Nervous system / Patients / Platelets / Risk factors / Scientific imaging / Sulfates / Thrombocytopenia / Thrombocytopenia - pathology / Toxicity / Transmission electron microscopy / Whole genome sequencing / Wilson disease / Wilson's disease / Zinc sulfate