Familial dysalbuminemic hyperthyroxinemia (FDH)1 is a well-characterized condition associated with increased circulating total thyroxine (T4) concentrations and normal physiological thyroid function. It is caused by mutations in the ALB (albumin) gene that increase the affinity of albumin for T4 by approximately 60-fold. When measured by equilibrium or symmetric dialysis, the free T4 (FT4) value is characteristically within the reference interval. Assays that rely on the competition of a T4 analog with unbound T4 in the sample can give spuriously high results in FDH patients, because albumin binding of the T4 analog is enhanced by the FDH mutation. “Two step” methods avoid this problem. Such assay methods are expected to give FT4 results within the reference interval in FDH patients, but this expectation has been questioned. Thyroid-function tests, including 1- and 2-step methodologies, were examined in 4 affected individuals from different families who had their FDH diagnoses proved genetically by DNA sequencing of exon 7 of the ALB gene. A diagnosis of FDH can be excluded by means of biochemical methods and by albumin genotyping. Because all mutations that have been associated with FDH to date involve residue 218 (242 with the signal peptide) in the albumin molecule, molecular genetic testing is comparatively simple and returns an unambiguous result.
Familial dysalbuminemic hyperthyroxinemia: a persistent diagnostic challenge
MACCHIA, ENRICO;
2009-01-01
Abstract
Familial dysalbuminemic hyperthyroxinemia (FDH)1 is a well-characterized condition associated with increased circulating total thyroxine (T4) concentrations and normal physiological thyroid function. It is caused by mutations in the ALB (albumin) gene that increase the affinity of albumin for T4 by approximately 60-fold. When measured by equilibrium or symmetric dialysis, the free T4 (FT4) value is characteristically within the reference interval. Assays that rely on the competition of a T4 analog with unbound T4 in the sample can give spuriously high results in FDH patients, because albumin binding of the T4 analog is enhanced by the FDH mutation. “Two step” methods avoid this problem. Such assay methods are expected to give FT4 results within the reference interval in FDH patients, but this expectation has been questioned. Thyroid-function tests, including 1- and 2-step methodologies, were examined in 4 affected individuals from different families who had their FDH diagnoses proved genetically by DNA sequencing of exon 7 of the ALB gene. A diagnosis of FDH can be excluded by means of biochemical methods and by albumin genotyping. Because all mutations that have been associated with FDH to date involve residue 218 (242 with the signal peptide) in the albumin molecule, molecular genetic testing is comparatively simple and returns an unambiguous result.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
