Hereditary Hyperferritinemia-Cataract Syndrome in 3 Generations of a Family in East Tennessee

Hereditary hyperferritinemia and cataracts syndrome (HHCS) without iron overload is a syndrome first identified less than 3 decades ago. While investigators have dissected the gene where several responsible mutations reside, it remains a relatively unknown genetic disorder to clinicians. The result is often an expensive, invasive evaluation for iron overload, followed by a well-intended prescription for a series of phlebotomies that delivers morbidity instead of benefit. We present a father with an elevated ferritin and heterozygosity for H63D HFE mutation whose clinical course followed this path. His treatment rendered him symptomatic from iron deficiency with no reduction in his ferritin. On re-evaluation, a review of his past medical history clarified the cataract surgery noted in his record had occurred at a young age. Furthermore, one of his daughters required cataract surgery as a teenager. With this information, we strongly suspected HHCS. His phlebotomies were discontinued, and within weeks, his iatrogenic iron deficiency resolved and his health returned to normal.

IDENTIFIKASI MUTASI H63D GEN HFE PADA KELAINAN HBE

The H63D HFE mutation has been reported to be responsible for primary haemochromatosis. The allele frequency in Indonesianpopulation is about 2.8%. Co inheritance between H63D mutation and hemoglobin disorders such as Thalassemia may increase theseverity of iron overload. Nevertheless, the coinheritance of this mutation with HbE disorder is the most common hemoglobin disorderin Indonesia and the gene frequency have not been reported especially in Javanese ethnic. To identify the presence and the frequency ofH63D HFE mutation in HbE disorder among Javanese ethnic. A cross sectional study involved 24 Javanese individuals who consist of21 HbE heterozygotes (HbAE) and 3 HbE homozygotes (HbEE) subjects. The subjects were screened for H63D mutation by digestion ofPCR products with MbO I restriction endonuclease. The genotype frequency for wt/wt was 95.24% in HbAE, 100% in HbEE and for wt/H63D was 4.76% in HbAE. The allele frequency for H63D HFE mutation was 2.08% in total sample of HbE. The allele frequencies inHbAE and HbEE individual were 2.38% and 0%, respectively. H63D HFE mutation is found in 24 Javanese ethnic individual with HbEdisorder. However, the allele frequency of H63D HFE mutation is low and almost similar to the allele frequency of H63D HFE mutationin Indonesian population.

HFE MUTATIONS AND IRON OVERLOAD IN PATIENTS WITH ALCOHOLIC LIVER DISEASE

ContextAlcoholic liver disease (ALD) is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE) gene mutations and the severity of liver disease in alcoholic patients.ObjectivesTo compare the prevalence of mutations in the hemochromatosis (HFE) gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity.MethodsLiver biopsy specimens were obtained from 63 ALD patients (during routine treatment) and 52 healthy controls (during elective cholecystectomy). All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations). Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis.ResultsALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05), but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI): 2.09-142.34, P = 0.008). However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003).ConclusionsALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, the presence of at least one HFE mutation increases the risk of having excessive liver iron stores but has no detectable effects on liver disease activity or severity.