Influence of Methodology on the Detection and Diagnosis of Congenital Analbuminemia

Abstract

Congenital analbuminemia is a rare recessive inherited disorder characterized by an absence or very low concentrations of serum albumin (1)(2). The diagnosis of analbuminemia is suggested by persistent hypoproteinemia with adequate hepatic function and a lack of evidence for either a renal or gastrointestinal protein loss. The diagnosis is typically confirmed by serum protein electrophoresis that depicts an absence of an albumin band (3). Rapid diagnosis of analbuminemia is appealing because patients can be subjected to extensive and prolonged testing to ascertain the cause of their apparent protein-losing disorder. Unfortunately, the diagnosis of analbuminemia may be delayed by clinically misleading laboratory results generated by tests of analytes that are usually bound to albumin, e.g., calcium (4) and thyroxine (5), and tests sensitive to the concentration of albumin in the matrix, e.g., some free thyroxine immunoassays (6)(7). In particular, rapid diagnosis of analbuminemia would be delayed if the method for serum albumin falsely reports the presence of albumin. The most commonly used serum albumin assays in clinical laboratories rely on dye-binding techniques (8). Characteristically, these methods accurately measure the concentration of serum albumin near the limits of the reference range. In conditions such as nephrotic syndrome, the serum albumin and the albumin:globulin ratio are low. Under these conditions, results of the bromcresol green (BCG) methods can be falsely inflated (9)(10)(11)(12)(13)(14)(15) and bromcresol purple-binding methods prone to falsely lowered results (16), although reagent manufacturers have adopted many variations of the dye-binding albumin methodology in an attempt to assure accuracy. Dye-binding albumin methods would likely be used to initially assess albumin status in undiagnosed patients with analbuminemia. Dye-binding albumin methods have falsely indicated the presence of albumin in analbuminemia in a rat model (17) and in a …