Patients with increased serum ferritin (1.5× upper limit of normal, >300ng/mL in females, >450ng/mL in males – values adopted from the Hemochromatosis and Iron Overload Screening Study2) and increased transferrin saturation (>45% in females, >50% in males) were enrolled in our study, for three consecutive years. Genetic testing for C282Y/H63D/S65C mutations of the HFE gene was performed by polymerase chain reaction. Standard biochemical markers of iron status, including serum ferritin and transferrin saturation, were obtained. Other laboratorial data included complete blood count, fasting glucose, liver function tests, lipid profile and serology for hepatitis B and C. Also, baseline demographic and clinical characteristics (with quantification of alcohol consumption) were recorded. Chronic renal disease, shunts, chronic haemolytic anemia, thalassemia major, sideroblastic or spur cell anemia, parenteral iron overload and porphyria cutanea tarda were excluded.

230 consecutive patients fulfilled the inclusion criteria, and were enrolled in our study. After HFE genetic analysis, the H63D homozygous mutation was identified in 6.96% (n=16) of the individuals. The mean age was 53.8 years (28–76), and ten (62.5%) were male. In this group, we found median value of serum ferritin of 550.3ng/mL and transferrin saturation of 57.6%.

Other causes of liver disease were found in 15: Non-Alcoholic Fatty Liver (NAFLD) in 8 patients, chronic alcohol consumption (>60g/day) in 3, chronic Hepatitis B in 3 and C in 1 patient. One patient with H63D homozygosity was negative for other hepatic diseases, viral infections, alcohol abuse and NAFLD.

It has been suggested that the H63D mutation contributes to iron overload, increasing serum iron and transferrin, and that its relationship with hemochromatosis is independent.3,4

In our study, H63D+/+ mutation in the HFE gene was detected in 6.96% of our cohort of patients with iron overload. Underlying causes were found in 93.7% such as NAFLD, chronic alcohol consumption and chronic hepatitis B and C. These data confirm the association between hyperferritinemia and these conditions, especially fatty liver. However it does not clarify whether siderosis was related to the underlying disease, namely steatosis, rather than homozygosity for the H63D mutation. Therefore, co-morbid factors may complicate the interpretation of data in population studies of the expression of H63D homozygosity.

In one patient, however, the investigation for other causes was negative, and H63D homozygosity may have played a role. The causative role of H63D+/+ mutation in HH or iron overload has been demonstrated,3 but with less penetrance and a considerable variation of phenotypic expression.5 Environmental factors, variable gene penetrance or other gene mutations may explain the variable phenotypic expression of H63D homozygosity.

None declared.

None declared.