Acute Deep Venous Thrombosis Unmasking Underlying Wilson’s Disease: Case Report

Abstract

Introduction: Wilson’s disease (WD), also known as hepato-lenticular disease, is an autosomal recessive disorder of copper excretion and can clinically present with hepatic, neurological, and psychiatric manifestations, which makes the diagnosis challenging in most of the cases. We present a case whose atypical presentation led to the unmasking of his underlying WD. Case Report: A 32-year-old male, recently diagnosed with type II diabetes mellitus, presented with pain and swelling of right lower extremity. On detailed history, the patient mentioned having a 3-month history of intention tremors, sialorrhea, hypophonia, progressive micrographia, and family history of a second-degree relative having WD. He had advanced intension tremors, cogwheel rigidity in the upper extremities, and olfactory dysfunction. His laboratory investigations showed D-dimer of 4,335 units, elevated PT (16.5 sec) and INR (1.8), and low albumin level (3.0 gm/dl) with normal liver enzymes. Right popliteal acute deep venous thrombosis (DVT) was confirmed by Doppler US. MRI brain showed cortical and cerebellar atrophy. MRI abdomen showed liver cirrhosis, mild splenomegaly, and small esophageal varices. Extensive work-up proved the diagnosis of WD by low serum copper level of 60 mcg/dL, low serum ceruloplasmin level of 15 mg/dL, and high 24-hour urine copper of 211 mcg. Liver biopsy showed macrovascular steatosis less than 5%, grade 3 portal and periportal chronic inflammation, grade 1-2 lobular inflammation, and stage 2 portal fibrosis with intact architecture and negative iron stain. Chemical quantification of copper in the liver biopsy was 219 ug/g drywt. Discussion: WD is caused by mutation of ATP7B gene on long arm of chromosome 13, which codes for a protein responsible for incorporating excess copper into ceruloplasmin to be excreted from the body. Subsequently, this leads to accumulation of copper in several organs, mainly the liver, brain, and cornea, and inevitably leads to progressive liver and neurological dysfunction. Hepatic manifestations range from asymptomatic biochemical abnormalities to acute hepatitis or chronic hepatitis and cirrhosis. Neurological manifestations include dysarthria, dystonia, tremors, or Parkinson’s-like manifestations. Less commonly, WD may present with cerebellar manifestations. Our patient had manifestations of cerebellar involvement as well as Parkinsonian features. This case presents a unique initial presentation of WD in the form of unprovoked DVT secondary to the hypercoagulable state, complicating chronic liver disease. As far as we know, DVT has not been reported to be one of the presenting complications of WD especially in patients without advanced liver cirrhosis.