Alterations in the Plasma Protein Expression Pattern in Congenital Analbuminemia—A Systematic Review

Abstract

Albumin is a highly abundant plasma protein with multiple functions, including the balance of fluid between body compartments and fatty acid trafficking. Humans with congenital analbuminemia (CAA) do not express albumin due to homozygosity for albumin gene mutation. Lessons about physiological control could be learned from CAA. Remarkably, these patients exhibit an apparently normal lifespan, without substantial impairments in physical functionality. There was speculation that tolerance to albumin deficiency would be characterized by significant upregulation of other plasma proteins to compensate for analbuminemia. It is unknown but possible that changes in plasma protein expression observed in CAA are required for the well-documented survival and general wellness. A systematic review of published case reports was performed to assess plasma protein pattern remodeling in CAA patients who were free of other illnesses that would confound interpretation. From a literature search in Pubmed, Scopus, and Purdue Libraries (updated October 2022), concentration of individual plasma proteins and protein classes were assessed. Total plasma protein concentration was below the reference range in the vast majority of CAA patients in the analysis, as upregulation of other proteins was not sufficient to prevent the decline of total plasma protein when albumin was absent. Nonetheless, an impressive level of evidence in the literature indicated upregulated plasma levels of multiple globulin classes and various specific proteins which may have metabolic functions in common with albumin. The potential role of this altered plasma protein expression pattern in CAA is discussed, and the findings may have implications for other populations with hypoalbuminemia.

Performance evaluation of different albumin assays for the detection of analbuminemia

“…Carbamylation of albumin, acute phase protein expression levels, and uremic toxins are also potential confounders of BCG dye performance that exhibit altered levels in various health conditions [ 12 , 22 , 24 ]. It is possible that this worsened performance of the assay also occurs in analbuminemic plasma as a moderately elevated α2-globulin expression is noted in CAA patients [ 25 ].…”

“…Nonetheless, it is a significant concern that unidentified substances accumulating in plasma in different patient populations could alter the behavior of BCP reagents [ 10 , 11 , 27 ]. The plasma proteome remodeling in both humans with CAA [ 25 ] and Alb -/- mice [ 20 , 21 ] is a concern in this regard. In both species, analbuminemia leads to higher expression of multiple proteins, including fibrinogen [ 20 , 25 ], and this high fibrinogen expression may lead to turbidity and thus improper spectrophotometer performance.…”

“…The plasma proteome remodeling in both humans with CAA [ 25 ] and Alb -/- mice [ 20 , 21 ] is a concern in this regard. In both species, analbuminemia leads to higher expression of multiple proteins, including fibrinogen [ 20 , 25 ], and this high fibrinogen expression may lead to turbidity and thus improper spectrophotometer performance. It should also be noted that in both BCG and BCP assays, bovine serum albumin was used as the standard for quantitation of samples.…”

Combining albumin deficiency and acute exercise reduces hepatic lipid droplet size in mice

“…The present finding of low LD content in Alb −/− liver is in line with a previous study where Alb −/− mice manifested alleviated hepatic steatosis from obesity induced by a high fat diet [ 36 ]. It should also be noted that in human subjects with a genetic disorder called congenital analbuminemia (CAA), no or very low albumin level is detected in plasma [ 46 ]. These patients can lead a normal life and exhibit some modest changes in the expression of other proteins in plasma.…”

“…These patients can lead a normal life and exhibit some modest changes in the expression of other proteins in plasma. Although plasma proteins like globulins are elevated in patients with CAA, the overall protein level is not well compensated, such that the total plasma protein concentration is lower than normal [ 46 ]. This agrees with the findings on Alb −/− mice [ 17 ].…”