Isa Hasan M, Alahmed Fawzeya A, Busehail Maryam Y, Isa Zahra H, Abdulla Kawthar M
Department of Pediatrics, Arabian Gulf University, Manama, BHR.
Department of Pediatrics, Salmaniya Medical Complex, Manama, BHR.
Cureus. 2024 Oct 18;16(10):e71805. doi: 10.7759/cureus.71805. eCollection 2024 Oct.
Introduction Wilson disease (WD) is a rare inherited autosomal recessive disorder caused by a mutation in the gene. This mutation affects copper metabolism, leading to the accumulation of copper in the liver, brain, cornea, and other tissues. If not treated, WD can lead to significant morbidities. This study aimed to display the prevalence, clinical presentations, diagnosis, treatment, and outcome of WD in Bahrain. Methods This is a retrospective cohort study of patients diagnosed with WD in the Department of Pediatrics, Salmaniya Medical Complex, Manama, Kingdom of Bahrain, from March 2002 to July 2024. The diagnosis of WD was based on clinical presentations, laboratory markers, radiological imaging, and genetic testing. Results Up to July 2024, eight patients from four families were diagnosed with WD in Bahrain. Accordingly, the prevalence of WD was 1.7 patients per 100,000 (0.002%). Parental consanguinity was noted in all families. Males were equal to females (n=4, 50% each). The mean age at presentation was 13 ± 3.6 years, ranging from 9 to 21 years. Three patients (37.5%) presented with hepatic manifestations, two (25%) with neurological manifestations, and three (37.5%) were detected upon family screening. Kayser Fleischer (KF) rings were found in two (25%) patients via slit lamp examination. Of the seven patients with available data, five (71.4%) had low serum copper, six (85.7%) had low serum ceruloplasmin, and six (85.7%) had high 24-hour urinary copper. Genetic testing was positive for the gene variants in all patients, of which four members of one family had a novel mutation. Abdominal ultrasound revealed hepatic cirrhosis in four (50%) patients, increased hepatic echogenicity in five (62.5%), splenomegaly in three (37.5%) patients, and ascites in one (12.5%) patient. Brain magnetic resonance imaging (MRI) was positive in three (50%) out of six patients. All patients received copper chelating therapy. Six (75%) patients survived; one of them underwent living-related liver transplantation due to rapidly progressive neurological symptoms. Two (25%) patients died due to hepatic failure and encephalopathy. Conclusion WD is a rare disorder in Bahrain. This study presents eight patients with WD from four families. Five patients were symptomatic at presentation, while three were diagnosed upon genetic family screening. Hepatic manifestations were the most common presentation, followed by behavioral changes and neurological symptoms. Two patients had KF rings, while three had classical brain MRI findings. Genetic testing served as a confirmatory diagnostic tool that revealed a diversity of variants causing the disease, of which one variant was a novel mutation. Despite oral chelating therapy, morbidity and mortality remain high in patients with WD.
引言
威尔逊病（WD）是一种罕见的常染色体隐性遗传疾病，由该基因的突变引起。这种突变影响铜代谢，导致铜在肝脏、大脑、角膜和其他组织中蓄积。若不治疗，WD可导致严重疾病。本研究旨在展示巴林WD的患病率、临床表现、诊断、治疗及预后。
方法
这是一项回顾性队列研究，研究对象为2002年3月至2024年7月在巴林王国麦纳麦萨勒曼尼亚医疗中心儿科诊断为WD的患者。WD的诊断基于临床表现、实验室指标、影像学检查和基因检测。
结果
截至2024年7月，巴林有来自四个家庭的8名患者被诊断为WD。因此，WD的患病率为每10万人中有1.7例患者（0.002%）。所有家庭均存在父母近亲结婚情况。男性和女性人数相等（均为4例，各占50%）。发病时的平均年龄为13±3.6岁，范围为9至21岁。3例患者（37.5%）表现为肝脏症状，2例（25%）表现为神经症状，3例（37.5%）是在家族筛查时被发现。通过裂隙灯检查，在2例（25%）患者中发现了凯-弗环（KF环）。在有可用数据的7例患者中，5例（71.4%）血清铜水平低，6例（85.7%）血清铜蓝蛋白水平低，6例（85.7%）24小时尿铜水平高。所有患者的基因检测均显示该基因突变阳性，其中一个家庭的4名成员有一个新的突变。腹部超声显示4例（50%）患者有肝硬化，5例（62.5%）肝脏回声增强，3例（37.5%）患者脾肿大，1例（12.5%）患者有腹水。6例患者中有3例（50%）脑磁共振成像（MRI）呈阳性。所有患者均接受了铜螯合治疗。6例（75%）患者存活；其中1例因迅速进展的神经症状接受了活体亲属肝移植。2例（25%）患者因肝衰竭和脑病死亡。
结论
WD在巴林是一种罕见疾病。本研究报告了来自四个家庭的8例WD患者。5例患者发病时有症状，3例是在基因家族筛查时被诊断出来的。肝脏症状是最常见的表现，其次是行为改变和神经症状。2例患者有KF环，3例有典型的脑MRI表现。基因检测作为一种确诊诊断工具，揭示了导致该疾病的多种变异，其中一种变异是新的突变。尽管进行了口服螯合治疗，但WD患者的发病率和死亡率仍然很高。
