Familial dysalbuminemic hyperthyroxinemia: 2 Indian cases with a novel ALB variant (p.Asn415Ile) identified in one

TL;DR

Two Indian families with a rare condition affecting thyroxine levels are reported, including a new genetic variant and differences in lab test results.

Contribution

A novel ALB variant (p.Asn415Ile) is identified, along with insights into immunoassay performance in FDH.

Findings

A novel heterozygous ALB variant (p.Asn415Ile) was identified in one family with FDH.

The Abbott ARCHITECT immunoassay showed minimal interference in measuring thyroxine levels in FDH cases.

Case 2 had an 11-13-fold increase in total thyroxine levels on most assays except Ortho VITROS.

Abstract

Familial dysalbuminemic hyperthyroxinemia (FDH) is a rare condition caused by pathogenic ALB variants, typically involving Arg242. We describe 2 Indian families with FDH. Case 1 showed elevated total (TT4) and free thyroxine (fT4) with normal thyroid-stimulating hormone (TSH). Her 2 children displayed a similar pattern. All 3 had ∼2-6-fold TT4 and 2-4-fold fT4 elevations on Roche COBAS and Beckman ACCESS assays, while Ortho VITROS reported low-normal fT4 and Abbott ARCHITECT showed minimal or no hormone elevation. Genetic analysis identified a novel heterozygous ALB variant, p.Asn415Ile. Case 2 was evaluated after markedly high TT4 was detected during routine screening. He demonstrated 11-13-fold TT4 elevation on most assays, except Ortho VITROS, and only a modest increase on Abbott ARCHITECT. Genetic testing confirmed the p.Arg242Ser ALB variant. To conclude, we report a novel ALB variant and show that Abbott ARCHITECT exhibits the least assay interference among the contemporary immunoassay platforms in FDH.