Severe iron overload with a novel aminolevulinate synthase mutation and hepatitis C infection. A case report

Area of Science:

• * Genetics and Molecular Biology
• * Gastroenterology and Hepatology
• * Cardiology

Background:

• * Hereditary hemochromatosis is a genetic disorder characterized by excessive iron absorption and storage.
• * Common genetic mutations (HFE, TFR2, SLC40A1, HAMP, HJV) explain most hemochromatosis cases.
• * Chronic hepatitis C infection can exacerbate iron overload and liver disease progression.

Observation:

• * A 55-year-old male presented with severe hemochromatosis, including cirrhosis, cardiomyopathy, arrhythmia, hypogonadism, diabetes, and skin hyperpigmentation.
• * The patient required 50 phlebotomies and a combined heart-liver transplant due to disease severity.
• * Standard genetic testing for known hemochromatosis genes was negative.

Findings:

• * Genetic analysis revealed a novel mutation in the iron-responsive element of the ALAS2 gene.
• * No mutations were identified in HFE, TFR2, SLC40A1, HAMP, or HJV genes.
• * The ALAS2 mutation is implicated as a potential cause of severe iron overload.

Implications:

• * This discovery expands the genetic landscape of hemochromatosis, identifying ALAS2 as a potential causative gene.
• * The findings suggest a synergistic effect between the novel ALAS2 mutation and chronic hepatitis C in driving severe iron overload.
• * Further research into ALAS2's role in iron metabolism may lead to new diagnostic and therapeutic strategies for specific hemochromatosis subtypes.