A tale of two sisters

Area of Science:

• Hepatology
• Medical Genetics
• Gastroenterology

Background:

• Hereditary haemochromatosis (HH) is a common inherited disorder in Caucasian populations.
• Non-alcoholic steatohepatitis (NASH) is an increasingly frequent cause for abnormal liver function tests (LFTs).
• The HFE gene mutation C282Y is strongly associated with HH.

Observation:

• Two sisters with similar environmental backgrounds presented with abnormal LFTs and were found to be C282Y homozygotes.
• One sister exhibited clinical features consistent with hereditary haemochromatosis.
• The other sister developed non-alcoholic steatohepatitis.

Findings:

• This case report highlights the variable clinical manifestation of HFE gene mutations.
• The findings suggest potential non-penetrance of the C282Y mutation.
• Abnormal LFTs require thorough investigation irrespective of initial genetic testing results.

Implications:

• Genetic predisposition does not guarantee disease manifestation; environmental factors likely play a role.
• Clinicians must consider a broad differential diagnosis for abnormal LFTs.
• Comprehensive diagnostic approaches are essential for accurate patient management and treatment.