Pediatric Wilson’s disease: findings in different presentations. A cross-sectional study

Abstract

Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism that occurs due to mutations in the copper-transporting ATP7B gene. Impaired excretion of copper through bile and decreased incorporation into ceruloplasmin cause excessive copper accumulation in different organs, including the liver, brain and cornea. 1-5 WD typically begins with a presymptomatic period, during which copper accumulation in the liver causes subclinical hepatitis, and progresses to liver cirrhosis and development of neuropsychiatric symptoms. There is no single diagnostic test that can rule out or confirm WD with certainty. Because of the lack of such a test, the diagnosis needs to be based on a combination of clinical features and laboratory, neuroradiological and pathological findings and also on the results from genetic analysis. 5-10 Pharmacological treatment of WD has the aim of preventing further accumulation of copper, through either reducing its absorption or promoting its excretion in urine or bile, or both. 5,6 The indications for liver transplantation to cure WD include progressive liver failure, progressive neurological symptoms, complications from portal hypertension (despite medical and dietary therapy) and acute liver failure. 5,6 There are not many detailed studies investigating pediatric WD series in the literature. 5-10 In the present study, we aimed to evaluate clinical presentations and laboratory findings among 64 children who were diagnosed with WD in our clinic over a nine-year period, and to determine their response to treatment and their prognosis from the follow-up.

Pediatric Wilson's Disease: Phenotypic, Genetic Characterization and Outcome of 182 Children in France

“…Indeed, in our cohort, many patients did not have an elevated urinary copper excretion (basal or after DP), neither high liver copper nor a KF ring, some patients even had normal ceruloplasmin levels. These equivocal findings have been well described in the literature (7,(11)(12)(13)(14)(15)(16)(17)(18) and highlight the importance of the use of clinical scores, and the value of genetic testing for mutations identification. Diagnosis of neurologic WD in children is even more complicated and a high index of suspicion is necessary since symptoms can be very varied and subtle.…”

“…For 19 (10%) patients, basal UCE was below 1.6 μmol/24 hours. The latter patients with low UCE had a median age of 9 years (1–18), 14 of 19 (73.7%) were H patients, 4 of 19 (21.1%) were AS patients, and 1 of 19 (5.3%) was an N patient. For five (2.7%) patients ages 1–6 years, basal UCE was <0.6 μmol/24 hours: two of five (40.0%) were H patients with mild elevation of transaminases diagnosed after family screening and three of five (60.0%) were AS patients.…”

“…Among them, four of six patients had Trientine as first‐line treatment and two of six had DP. The median time between diagnosis and LT was 7 (2–31) months, the mean Unified Wilson's Disease Rating Scale (UWDRS) was 26.8 ± 22.9 at diagnosis and 90 ± 23.1 before LT. Improvement after LT was satisfactory.…”

Nhận xét kết quả điều trị các thể lâm sàng bệnh Wilson ở trẻ em

“…Tuy nhiên trong nghiên cứu này, chúng tôi có tới 9 trong số 13 bệnh nhân tổn thương gan cấp hồi phục sau điều trị nội khoa mà không cần ghép gan. Kết quả này của chúng tôi cũng tương tự báo cáo của Güngör và CS [10] có 4 trong số 7 bệnh nhân suy gan tối cấp vẫn sống nhờ điều trị nội khoa mà không cần ghép gan.…”

Wilson’s Disease Presenting with Generalized Tonic-Clonic Seizure and Cerebellar Dysfunction

“…Wilson's disease (WD) is an infrequent autosomal recessive disturbance of copper metabolism which happens as a result of mutations in the copper-transporting ATP7B gene. 1 Increased free copper levels in different organs cause injury to them, with broad-ranging clinical manifestations dominated by signs of liver and brain injury, especially of the basal ganglia and cerebellum. 2 Abnormal movements such as tremor, dystonia, bradykinesia, and chorea, accompanied with difficulty swallowing, difficulty speaking and poor articulation, and excessive salivation are the chief neurologic manifestations.…”