Common clinical presentations of Wilson disease:
Owing to multiple genetic mutations of the ATP7B gene, the clinical presentations can be highly variable. The hepatic form presents before age 18 years and the neuropsychiatric form in early adulthood (age 20 to 30 years); a late-onset form also exists. Manifestations include the following:
- Liver disease: abnormal liver-associated enzymes are seen in over 95% of cases. Liver disease is the initial presentation in 50% of cases and can manifest as asymptomatic transient hepatitis to fulminant hepatitis, chronic active hepatitis, and cirrhosis.
- Neuropsychiatric disease: the most common manifestations are varying tremors, rigidity, and dystonia caused by basal ganglion degeneration. Psychiatric disorders such as mood disturbances, neurosis, hypophonia, and personality changes occur in up to 33% of cases. These manifestations tend to occur later than the hepatic presentation, but abnormal liver transaminases and Kayser–Fleischer rings are invariably seen in these patients.
- Eyes: Kayser–Fleischer rings are caused by granular deposits in Descement membranes; present in 95% of patients with and 50% to 60% of patients without neurologic symptoms
- Hematologic: Coombs-negative hemolytic anemia
- Kidneys: tubular dysfunction, Fanconi syndrome
- Fertility: amenorrhea, infertility
- Musculoskeletal: osteoarthritis, osteopenia
Musculoskeletal manifestations of Wilson disease:
Musculoskeletal manifestations occur in 50% of patients but are rarely the presenting symptom because all patients have other manifestations of Wilson disease. Pain and swelling of the MCPs, wrists, elbows, shoulders, knees, and hips resembling hemochromatosis may occur, although asymptomatic radiographic changes are equally as common. Radiographically, subchondral and cortical fragmentation, as well as marginal, subchondral, and central bony sclerosis of the wrist, hand, elbow, shoulder, and knee, help to distinguish this arthropathy from primary osteoarthritis. Unlike hemochromatosis, involvement of the hip and MCP joints is uncommon. Less common radiographic findings include osteochondritis dissecans, chondrocalcinosis, chondramalacia patellae, and vertebral wedging. Generalized osteoporosis or osteomalacia may be present as a result of Fanconi syndrome or renal tubular acidosis, both of which are common in Wilson disease.