Early age‐of‐onset iron overload and homozygosity for the novel hemojuvelin mutation HJV R54X (exon 3; c.160A→T) in an African American male of West Indies descent

Abstract

An African American male of West Indies descent was diagnosed to have elevated transferrin saturation, hyperferritinemia, severe iron deposition in hepatocytes, and hepatic cirrhosis at age 4. He was treated with serial phlebotomy to maintain a normal serum ferritin concentration thereafter. We evaluated him at age 23 and confirmed that he had normal serum ferritin levels, severe iron deposition in hepatocytes, hepatic cirrhosis, and portal hypertension. He did not have endocrinopathy, cardiomyopathy, or arthropathy. He was homozygous for the novel hemojuvelin (HJV) premature stop-codon mutation R54X (exon 3; c.160A-->T). He did not have either HFE C282Y, H63D, or S65C, or deleterious coding region mutations of SLC40A1, TFR2, or HAMP. His erythrocyte measures and hemoglobin electrophoresis were consistent with alpha-thalassemia trait. We conclude that homozygosity for HJV R54X accounts for his severe, early age-of-onset hemochromatosis; his phenotype was probably modified by serial phlebotomy therapy.

Appropriate Clinical Genetic Testing of Hemochromatosis Type 2–4, Including Ferroportin Disease

“… 50 The earliest age at which patients present with symptoms of iron overload associated with HJV mutations was age 4 in an African American patient with the homozygous nonsense mutation p.R54X. 53 …”

“…50 The earliest age at which patients present with symptoms of iron overload associated with HJV mutations was age 4 in an African American patient with the homozygous nonsense mutation p.R54X. 53 Originally known as HFE2, HJV was first mapped by Papanikolaou et al, from a Greek family. 16 Six candidate mutations were identified based on polymorphisms compared to controls in ten Greek families, one Canadian family and one French family in juvenile hemochromatosis patients without p.C282Y mutations.…”