ATP7B gene


1. The disease

Wilson disease is an inherited hepatolenticular degeneration due to abnormal copper metabolism caused by mutations in ATP7B gene. This disorder is inherited in an autosomal recessive pattern – a mutation must be present in the copies inherited from both the mother and the father – for the disease to manifest itself. The metabolic error comprises reduced excretion of copper into bile, resulting in a gradual accumulation of copper in the liver and, secondarily, in the brain, kidneys and eye.

2. The symptoms

Wilson disease can present with hepatic, neurologic or psychiatric disturbances, or even as a combination of these, in individuals ranging from age of three years to older than 50 years; symptoms vary among and within families. Lack of early signs or symptoms does not exclude the diagnosis.

  • Hepatic symptoms generally present between 8 and 20 years of age. The presentation can be acute and severe with hepatitis, jaundice, and liver failure. Untreated patients can present liver cirrhosis, while others develop subclinical liver disease.
  • Neurological symptoms usually develop in the second or third decade. Symptoms include movement disorders (tremors, poor coordination, loss of fine-motor control, chorea, choreoathetosis) or rigid dystonia (mask-like facies, rigidity, gait disturbance, pseudobulbar involvement).
  • Psychiatric disturbance includes depression, disorganization of personality, neurotic behaviors, and, occasionally, intellectual deterioration.
  • Patients with high levels of copper storage in the body might present characteristic copper deposition in the cornea, known as Kayser-Fleischer rings.

3. Actions to take in case of early diagnosis

  • Infants with a positive genetic test (having 2 pathogenic variants or 2 copies of a single pathogenic variant in the ATP7B gene) should continue breastfeeding.
  • Genetic analysis is more reliable than laboratory investigations of copper metabolism, which cannot always distinguish between carriers and young patients who still have a low copper intake.
  • Wilson disease is a lifelong condition that requires lifetime management with copper chelating agents or zinc that should be initiated as soon as possible and regular follow-up with a metabolic disease specialist and a multidisciplinary approach to care, including paediatrics, neurology, genetics and nutrition.
  • Lifetime surveillance should be done with routine monitoring that includes serum copper and ceruloplasmin, liver biochemistries, complete blood count, urinalysis, and physical examination including neurologic assessment.
  • The prognosis is excellent for patients who start treatment in presymptomatic or early stages of the disease (before severe tissue damage has occurred). The prognosis can still be good for those with more advanced disease, if aggressive treatment is instituted immediately after diagnosis.
  • Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

4. For more information

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