[Hereditary hyperferritinemia cataracts syndrome in a Spanish family caused by the A40G mutation (Paris) in the L-ferritin (FTL) gene associated with the mutation H63D in the HFE gene].

BACKGROUND AND OBJECTIVE: The cataract-associated increase in serum ferritin without any other data of iron overload is known since 1995 as hyperferritinemia-cataract syndrome (HHCS). More than 100 families have been described all around the world with this syndrome and more than 30 mutations in the L-ferritin (FTL) gene. We introduce a family from Madrid (Spain), with the disease phenotype and a genotype with the A40G mutation, named Paris, and besides carrier of the H63D mutation of the HFE gene.

PATIENTS AND METHOD: The proband and his first grade relatives were studied by determining the hemogram, biochemistry, iron metabolism and HFE gene mutations study, as well as by hepatic magnetic resonance imaging and oftalmologic study. Afterwards a molecular study of the coding region for the IRE (iron responsive element) of the FTL gene was done by sequencing.

RESULTS: The proband is a male with early cataracts and hyperferritinemia, heterozygous for the H63D and A40G mutations of the HFE and FTL genes, respectively. The mother has the same phenotype (hyperferritinemia and surgery for early cataracts) and genotype (H63D and A40G alleles in heterozygosis). On the other hand, the sister has no cataracts but has hyperferritinemia, is homozygous for H63D and heterozygous for A40G. The father is heterozygous for H63D, but lacks the A40G mutation and the HHCS phenotype.

CONCLUSIONS: The HHCS must be included in the differential diagnosis of the hyperferritinemias without iron overload. In turn, hyperferritinemia must be ruled out in an early cataract. The only treatment is ophthalmological, and phlebotomies must be avoided in a false hemochromatosis diagnostic when HFE gene mutations are associated, because of the poor tolerance for causing severe anemia.