Osteoarticular manifestations as initial symptoms of WD with novel compound heterozygote mutations in the ATP7B gene: a case report

Wilson disease (WD) is a rare autosomal recessive disease characterized by hepatic, neurologic and psychiatric, and variable manifestations. Skeletal and articular manifestations are usually overlooked at an early stage in WD patients, which have an effect on therapeutic outcome and prognosis. We report a 13-year-old girl of Chinese Han ethnicity with arthralgia and fracture as initial symptoms of WD. Laboratory tests showed her 1:80 of antinuclear antibodies (ANA). The patient was diagnosed with oligoarticular juvenile idiopathic arthritis (JIA) and treated with 10 mg of methotrexate (MTX) every week and diclofenac sodium every day. Her symptoms showed no improvement over 6 months and her medications were ceased. Then the patient presented to our department with a 3-week history dysarthria, gait abnormalities, dystonia and tremor. Kayser-Fleischer rings, serum ceruloplasmin and liver biopsy confirmed the diagnosis of WD. Genetic analysis was performed using SureSelect Clinical Research Exome v2 and then verified by bi-directional Sanger sequencing. We found that the patient carried a novel compound heterozygous mutation in ATPase copper transporting beta (ATP7B) on both chromosomes, which consist of a heterozygote of NM_000053.3 (ATP7B): c.3884C>T p. Ala1295Val and large fragment heterozygous deletion in exons 10–11 of ATP7B gene identified using multiplex ligation-dependent probe amplification (MLPA), to be inherited from her asymptomatic parents, respectively. The patient’s symptoms were relieved at the 1-year follow-up after treatment with D-penicillamine and oral zinc. This case highlights that WD should be taken into consideration in adolescents with unexplained joint pain, arthritis, and fracture of the large joints.