ATP7B Mutation Analysis: Wilson Disease, A Difficult to Diagnose Case

Area of Science:

• Genetics
• Metabolic Disorders
• Hepatology

Background:

• Wilson disease (WD) is an inherited metabolic disorder characterized by excessive copper accumulation in organs like the liver, brain, and eyes.
• Diagnosis typically relies on a combination of clinical findings and laboratory tests, often interpreted using the Wilson disease diagnostic index (WDDI).
• Atypical presentations and equivocal initial results can complicate diagnosis, necessitating advanced genetic testing.

Observation:

• A 9-year-old girl from a consanguineous family presented with chronic liver disease and portal hypertension, posing a diagnostic challenge.
• Initial investigations revealed low serum ceruloplasmin but normal urinary copper excretion and absent Kayser-Fleischer rings, making a definitive diagnosis difficult.
• The patient was homozygous for the c.3955C>T (p.Arg1319Ter) mutation in the ATP7B gene, a rare mutation leading to premature protein truncation.

Findings:

• ATP7B mutation analysis was crucial in establishing the diagnosis of Wilson disease in this complex case.
• The identified homozygous mutation, c.3955C>T (p.Arg1319Ter), explains the patient's phenotype and underscores the importance of genetic testing in WD diagnosis.
• This case highlights that Wilson disease can present with varied symptoms and normal urinary copper levels.

Implications:

• Genetic testing for ATP7B mutations is essential for diagnosing Wilson disease, especially in ambiguous cases.
• Early and accurate diagnosis through genetic analysis allows for timely treatment initiation, potentially preventing severe complications.
• Understanding rare ATP7B mutations contributes to a comprehensive knowledge base for diagnosing and managing Wilson disease globally.