Orphanet Journal of Rare Diseases · 10 authors, 6 centres
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This survey of 63 German university departments found that approximately 950 Wilson disease patients are seen annually, covering about one-third of the estimated national prevalence. Most departments follow international guideline recommendations for diagnosis and monitoring, but only 12% use a multidisciplinary approach and only 51% routinely apply the Leipzig diagnostic score. The authors recommend establishing larger, multidisciplinary centers to improve care for this rare disease.
**Background:** Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism caused by ATP7B gene mutations, leading to copper accumulation in the liver, brain, and other organs. Manifestations include hepatic abnormalities, neurologic symptoms (tremor, ataxia), psychiatric symptoms, and less commonly cardiomyopathy, renal abnormalities, hemolytic anemia, and pancreatitis. The estimated prevalence is approximately 1:30,000, corresponding to about 3,000 patients in Germany. Lifelong chelation therapy (D-penicillamine, trientine) or zinc salts are required to prevent fatal copper overload. Several international guidelines exist (AASLD, EASL, ESPGHAN), but data on actual medical care for WD patients in Germany are scarce.
**Methods:** In October 2021, a 20-item standardized questionnaire was mailed to 108 departments (pediatrics, neurology, gastroenterology/hepatology) across all 36 German university hospitals. A reminder letter was sent in January 2022, followed by phone calls to non-responders. Questions covered patient numbers, diagnostic practices (including use of the Leipzig score), monitoring frequency and investigations, treatment regimens, family screening, transition programs, pregnancy management, nutrition counseling, and liver transplantation. Descriptive statistical analysis was performed using SPSS (Version 28).
**Key Results:** Sixty-three of 108 departments (58%) returned the questionnaire, equally distributed among pediatrics (35%, n=22), neurology (32%, n=20), and gastroenterology (33%, n=21). An estimated 950 WD patients are seen annually across these departments, representing approximately one-third of the expected WD population in Germany. Only 12% (n=7/60) of departments reported a multidisciplinary outpatient clinic for WD. The median number of WD patients per department was 5 (IQR: 2–15); five departments saw >30 patients/year. For diagnosis, 51% (n=29/57) of departments routinely used the Leipzig score. Serum ceruloplasmin, serum copper, and 24-hour urinary copper excretion were determined by nearly all departments (100% each). Genetic ATP7B analysis was used by 100% of pediatric and neurology departments but only 60% of gastroenterology departments. Liver biopsy for hepatic copper content was performed in 100% of pediatric, 80% of gastroenterology, and 15% of neurology departments. For monitoring, 84% (n=46/55) of departments followed patients at least biannually. Liver enzymes (89%), INR (88%), and complete blood count (89%) were determined at least twice yearly by most departments; neurologic examinations were performed at least biannually by only 18% (n=10/54). Chelator therapy was paused before measuring 24-hour urinary copper excretion by 48% (n=24/50) of departments overall, but only 15% of pediatric departments versus 70% of neurology/gastroenterology departments. Zinc monotherapy was used regularly by 58% of pediatric departments but only 38% of neurology and 35% of gastroenterology departments. Among departments using monotherapy (n=33), mean proportions were D-penicillamine 72%, trientine 19%, and zinc salts 9%. Treatment reevaluation for possible dose reduction was performed by 81% (n=43/53) of departments, usually after 2 years (49%) or 2–5 years (26%). Family screening was performed by 84% (n=46/55) of departments. Structured transition programs existed in 27% (n=15/55). During pregnancy, 46% (n=11/24) of departments recommended dose reduction, while 25% (n=6/24) made no therapy adjustment. Only 14% (n=3/22) advised against breastfeeding. Professional nutrition counseling was offered by 63% (n=34/54) of departments. Liver transplantation was reported by 72% (n=13/18) of gastroenterology departments (median 3 patients, IQR: 2–5) but was uncommon in pediatrics (30%) and neurology (17%).
**Clinical Implications:** The study demonstrates that WD care at German university centers generally follows international guideline recommendations, with adequate monitoring frequency and diagnostic parameter use. However, critical gaps exist: only half of departments use the Leipzig diagnostic algorithm, multidisciplinary care is rare (12%), chelator cessation protocols before urinary copper measurement are inconsistently applied (48%), and pregnancy management varies substantially. The low patient volume in most departments (median 5 patients/year) raises concerns about expertise concentration. The authors recommend establishing larger, multidisciplinary centers and networks to standardize care and improve outcomes for WD patients. Limitations include a 58% response rate, potential reporting bias, anonymous responses preventing verification, and reliance on estimated rather than patient-level data.