Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon.
Pediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Biliary Atresia and Genetic Cholestasis, FILFOIE, ERN RARE LIVER, Bicêtre Hospital, Assistance Publique - Hôpitaux de Paris, Le Kremlin-Bicêtre.
J Pediatr Gastroenterol Nutr. 2021 Oct 1;73(4):e80-e86. doi: 10.1097/MPG.0000000000003196.
To describe a cohort of Wilson disease (WD) pediatric cases, and to point out the diagnostic particularities of this age group and the long-term outcome.
Clinical data of 182 pediatric patients included in the French WD national registry from 01/03/1995 to 01/06/2019 were gathered.
Diagnosis of WD was made at a mean age of 10.7 ± 4.2 years (range 1-18 years). At diagnosis, 154 patients (84.6%) had hepatic manifestations, 19 (10.4%) had neurological manifestations, and 9 patients (4.9%) were asymptomatic. The p.His1069Gln mutation was the most frequently encountered (14% of patients).Neurological patients were diagnosed at least 1 year after they presented their first symptoms. At diagnosis, the median urinary copper excretion (UCE) was 4.2 μmol/24 hours (0.2-253). The first-line treatment was d-penicillamine (DP) for 131 (72%) patients, zinc salts for 24 (13%) patients, and Trientine for 17 (9%) patients. Liver transplantation was performed in 39 (21.4%) patients, for hepatic indications in 33 of 39 patients or for neurological deterioration in 6 of 39 patients, mean Unified Wilson's Disease Rating Scale of the latter went from 90 ± 23.1 before liver transplantation (LT) to 26.8 ± 14.1 (P < 0.01) after a mean follow-up of 4.3 ± 2.5 years. Overall survival rate at 20 years of follow-up was 98%, patient and transplant-free combined survival was 84% at 20 years.
Diagnosis of WD can be challenging in children, particularly at the early stages of liver disease and in case of neurological presentation; hence the support of clinical scores and genetic testing is essential. Diagnosis at early stages and proper treatment ensure excellent outcomes, subject to good long-term treatment compliance. LT is a valid option for end-stage liver disease not responding to treatment and can be discussed for selected cases of neurological deterioration.
描述一组肝豆状核变性（WD）儿科病例，并指出该年龄组的诊断特点和长期预后。
收集了法国 WD 国家登记处 1995 年 3 月 1 日至 2019 年 6 月 1 日期间纳入的 182 例儿科患者的临床资料。
WD 的诊断平均年龄为 10.7±4.2 岁（1-18 岁）。诊断时，154 例（84.6%）患者有肝脏表现，19 例（10.4%）有神经系统表现，9 例（4.9%）无症状。最常见的突变是 p.His1069Gln（14%的患者）。神经系统患者在出现首发症状至少 1 年后才被诊断。诊断时，尿铜排泄中位数（UCE）为 4.2μmol/24 小时（0.2-253）。一线治疗为二巯丁二酸（DP）131 例（72%），锌盐 24 例（13%），曲恩汀 17 例（9%）。39 例（21.4%）患者行肝移植，其中 33 例因肝脏原因，6 例因神经恶化行肝移植，后者平均统一 Wilson 病评分从肝移植前的 90±23.1 降至肝移植后 26.8±14.1（P<0.01），平均随访 4.3±2.5 年后。20 年随访总生存率为 98%，患者和无移植生存率为 20 年 84%。
儿童 WD 的诊断具有挑战性，尤其是在肝脏疾病的早期阶段和神经系统表现时；因此，临床评分和基因检测的支持至关重要。早期诊断和适当治疗可确保良好的预后，但需长期治疗依从性良好。LT 是治疗无效的终末期肝病的有效选择，对选择的神经恶化病例可进行讨论。
