RESUMO
BACKGROUND: Familial dysalbuminemic hyperthyroxinemia (FDH) is a rare autosomal dominant disorder whose clinical characteristics remain incompletely understood, we investigated the role of albumin gene mutation in relation to miscarriage rate in a large pedigree of FDH followed up for 4 years. PATIENTS AND METHODS: The proband and extended family with unexplained miscarriage and hyperthyroxinemia were identified and genotypes in candidate genes and thyroid function tests (TFTs), including changes in TFTs during pregnancy were comprehensively assessed. We also evaluated the development and growth of children in this large FDH pedigree during four years follow-up. RESULT: The R218S variant in the albumin gene was identified in the proband and her relatives with hyperthyroxinemia who were diagnosed as FDH. Among the family members who underwent TFTs, 11 of 17 (65%) had similar changes in levels of thyroid hormone, with an estimated FDH heritability of 86%. Moreover, 32% (95% CI 16-54%) of FDH women experienced miscarriages at a rate that was substantially higher than the spontaneous abortion rate reported in the general population in China (7-14%). During the follow-up, results revealed that free triiodothyronine (fT3) and thyroid stimulating hormone (TSH) levels were normal during the entire gestational period; comparing to their age-adjusted peers, both FDH affected and FDH unaffected children in this pedigree appeared to have lower body weight and height. CONCLUSIONS: Albumin gene variant (R218S) not only causes FDH but also may be associated with a higher risk of miscarriages, although the growth of their children appears not to be affected by the age of 2 years.
