Hyperferritinemia-cataract syndrome associated to the HFE gene mutation. Two new Spanish families and a new mutation (A37T: "Zaragoza")

BACKGROUND AND OBJECTIVE: Nuclear congenital cataracts associated with hyperferritinemia--hereditary hyperferritinemia cataract syndrome (HHCS)--without clinical or biochemical signs of iron overload have been recently described in several Spanish families. This HHCS is associated with mutations in the gene of ferritin subunit L, located in chromosome 19. We describe 2 new families with HHCS, one of them presenting a new L-ferritin mutation (A37T: -Zaragoza-). PATIENTS AND METHOD: Patients and probands were studied according to the Anemia Unit protocol: complete blood count, biochemical profile (diabetes, hepatic and renal), hepatic serologies, iron metabolism (iron, transferrin, ferritin, transferrin saturation, reactive C protein) and mutation HFE gene studies (C282Y, H63D). All of them were sent to the Ophthalmology Service for cataract study. L-ferritin mutational scanning was performed by denaturing high performance liquid chromatography (DHPLC). Samples displaying an altered elution profile, as compared to a wild type control, were directly sequenced for the precise characterization of the L-ferritin mutation. RESULTS: Family A proband was a 54 year-old-female, with cataracts, ferritin level: 942 pg/I, transferrin saturation: 14%, HFE gen study: H63D/H63D; L-ferritin gene study: C33T mutation/-. Her two sons had cataracts, hyperferritinemia (1607, and 1188 pg/I, respectively), normal transferrin saturation (40% and 9%), HFE gene study: H63D/N; and L-ferritin gen study: C33T/-. Family B proband was a 39 year-old-female, with cataract, ferritin level: 636 pg/I, transferrin saturation: 25%, HFE gene study: H63D/N; and L-ferritin gene study: A37T/-. Her two sons, sister, brother and nephew, who were affected with A37T mutation, showed hyperferritinemia (883, 747, 835, 613 and 1396 pg/I) with normal transferrin saturation levels (17%, 34%, 25%, 18% and 24%); but the ferritin levels of those non-affected were normal (35 and 50 pg/I). CONCLUSIONS: HHCS is a dominant autosomic condition, with a possible world-wide distribution,which should be included in the differential diagnosis of hyperferritinemia studies. It is important to suspect it in order to avoid wrong treatment.