An Unexpected Smile: risus sardonicus and wing-beating tremor in a first office visit

Context: We present a noteworthy reminder of Wilson disease’s classical manifestations, which may become rarer in clinical practice as availability of genetic tests increases, allowing timely diagnosis and treatment. Case report: A 29 year-old woman developed progressive and asymmetric upper limb tremor and dystonia over 1 year, along with speech and feeding impairment in the last two weeks. Examination revealed segmental dystonia with risus sardonicus, open-jaw oromandibular and severe left arm dystonia, along with wing-beating tremor. Bilateral Kayser-Fleischer ring, low serum ceruloplasmin level, high urinary copper level, bilateral putaminal lesions on brain MRI and detection of ATP7B mutation confirmed Wilson disease (WD). A nasoenteric tube was inserted and D-penicillamine was started. Conclusion: This case illustrates the hallmark neuro-ophtalmological signs of WD: wing-beating tremor, risus sardonicus and Kayser-Fleischer ring. The former is probably associated with lesions in the dentato-rubro-thalamic pathway¹ and means a low frequency, high amplitude, posture-induced proximal arm tremor. Risus sardonicus means a fixed smile due to risorius muscle dystonia². Although it is a well-known manifestation of cephalic tetanus, it is also frequent in WD¹. Finally, the Kayser-Fleischer ring is caused by copper accumulation in the Descemet membrane and occurs in almost 100% of patients with neurological WD².

Wilson’s Disease: Diagnosis of Wilson’s Disease in Ethiopian Young Sisters

Background. Wilson’s disease is an inherited autosomal recessive disorder of copper metabolism. Clinical signs, biochemical parameters, histologic findings, and/or ATP7B genetic testing are required to diagnose Wilson’s disease. Case Presentation. 25-year-old and 22-year-old young women (siblings) presented to the University of Gondar Hospital, Northwest Ethiopia, with difficulty of keeping balance of 3-year duration and progressive extremity weakness of 5-year duration, respectively. Both siblings had visible ocular Kayser–Fleischer rings, low serum ceruloplasmin level and increased urinary copper content, ultrasound-evidenced cirrhotic liver disease, and axial T2-weighted MRI hyperintensities in basal ganglia, thalamus, and brainstem (midbrain and pons). Diagnosis of Wilson’s disease was established in both patients using a diagnostic scoring system proposed by “8th International Meeting on Wilson Disease and Menkes Disease, Leipzig (2001).” Treatment with D-penicillamine as a chelator and zinc sulphate as a metalothionein-inductor was started. Screening of their family members was recommended. Conclusion. Wilson’s disease, declared to be an orphan disease, requires clinical acumen of physicians and expensive investigation modalities for prompt recognition and is inaccessible as required, lifelong drugs for treatment.

Evaluation and grading of Kayser–Fleischer ring in Wilson disease by Scheimpflug camera

Purpose: Evaluation the anterior segment parameters of Wilson disease patients with Kayser–Fleischer ring, the diagnostic power of Scheimpflug imaging for Kayser–Fleischer ring and suggest a scoring system. Materials and Methods: A total of 44 eyes of 22 Wilson disease patients with Kayser–Fleischer ring and 40 right eyes of 40 healthy age matched subjects were enrolled to the study. Serum ceruloplasmin and urine copper/24 hours levels were recorded. Anterior segment parameters including steep and flat keratometry, corneal thickness at central, 2, 4, 6, 8 and 10 mm, anterior chamber angle width, volume and depth, corneal volume, pupillary diameter were evaluated by Scheimpflug imaging. Images of cornea were scored according to Kayser–Fleischer ring size. Results: Serum ceruloplasmin level was below 10 mg/dL in 17 patients and was 12, 18.5, 20, 22, 37 mg/dl in the remaining five patients. Urinary copper/24 hours was 249.55 ± 304.14 (23–1050) µg/day. Central corneal thickness and corneal thickness at 2 mm were statistically different ( p values 0.02, 0.04, respectively). Scheimpflug images apparently showed Kayser–Fleischer ring as a hyper-reflective band at the corneal endothelial surface. Kayser–Fleischer ring in 24 eyes was grade 1, 16 eyes were grade 2 and 4 eyes were grade 3. Conclusion: Scheimpflug imaging seems to be a helpful diagnostic tool for detecting and grading the Kayser–Fleischer ring. Corneal thickness in Wilson disease patients with Kayser–Fleischer ring tends to be higher, so that the possible affection in corneal thickness should be kept in mind for clinical evaluation of these patients.

Wilson disease: a diagnostic challenge in a patient with alcoholic liver disease

A 32-year-old man with alcoholic cirrhosis presented with worsening abdominal distension and jaundice. He was diagnosed with cirrhosis 2 years prior after a hospitalisation for acute liver failure, during which viral, autoimmune and metabolic workup was unrevealing. Heavy alcohol consumption was his only obvious risk factor for liver disease, so his decompensation was attributed to alcohol. At the present time, he was admitted with acute-on-chronic liver failure and acute renal failure. The severity of his presentation and the disproportionately mild elevation in alkaline phosphatase relative to his hyperbilirubinaemia prompted repeating a ceruloplasmin level, which, though previously normal, was now low, and eventually led to a diagnosis of Wilson disease (WD) with concomitant alcoholic liver disease. Clinicians must recognise limitations in ceruloplasmin and copper levels when screening for WD and maintain suspicion for WD in young patients, even if there is an already established aetiology of liver disease.

Cholangiocarcinoma in Wilson’s Disease – a Case Report

It has been suggested that hepatobiliary carcinomas are less frequent in Wilson’s disease (WD) than in liver diseases of other etiology. However, the protective role of copper against malignancies is debated. Only a few cases of cholangiocarcinoma (CCC) in WD have been published. Here we report on a case of a 47-year-old male H1069Q homozygous, Kayser-Fleischer ring positive WD patient with a low ceruloplasmin level who was followed up and treated with chelating agents throughout nine years. The patient presented with neurological symptoms and liver cirrhosis at diagnosis. Clinical symptoms regressed after the treatment initiation. Rapidly developed tumour metastases were found in the bones, lung and liver (without jaundice). Autopsy revealed cholangiocarcinoma as the primary tumour confirmed by strong CK7 positivity and glypican-3 negativity. The curiosity of the presented case is the very rapid development of CCC despite continuous chelating agent therapy.Abbreviations: CCC: cholangiocarcinoma; HCC: hepatocellular carcinoma; WD: Wilson disease.