Abstract
Congenital analbuminemia (CAA) is an inherited, autosomal recessive disorder with an incidence of 1:1,000,000 live birth. Affected individuals have a strongly decreased concentration, or complete absence, of serum albumin. The trait is usually detected by serum protein electrophoresis and immunochemistry techniques. However, due to the existence of other conditions in which the albumin concentrations are very low or null, analysis of the albumin (ALB) gene is necessary for the molecular diagnosis. CAA can lead to serious consequences in the prenatal period, because it can cause miscarriages and preterm birth, which often is due to oligohydramnios and placental abnormalities. Neonatally and in early childhood the trait is a risk factor that can lead to death, mainly from fluid retention and infections in the lower respiratory tract. By contrast, CAA is better tolerated in adulthood. Clinically, in addition to the low level of albumin, the patients almost always have hyperlipidemia, but they usually also have mild oedema, reduced blood pressure and fatigue. The fairly mild symptoms in adulthood are due to compensatory increment of other plasma proteins. The condition is rare; clinically, only about 90 cases have been detected worldwide. Among these, 53 have been studied by sequence analysis of the ALB gene, allowing the identification of 27 different loss of function (LoF) pathogenic variants. These include a variant in the start codon, frame-shift/insertions, frame-shift/deletions, nonsense variants, and variants affecting splicing. Most are unique, peculiar for each affected family, but one, a frame-shift deletion called Kayseri, has been found to cause about one third of the known cases allowing to presume a founder effect. This review provides an overview of the literature about CAA, about supportive and additional physiological and pharmacological information obtained from albumin-deficient mouse and rat models and a complete and up-to-date dataset of the pathogenic variants identified in the ALB gene.
Highlights
Congenital analbuminemia (CAA; OMIM # 616000) is an autosomal recessive disorder
The first twelve exons of ALB, with the exception of the two shortest, exons 2 and 6, were reported to contain at least one molecular defect resulting in CAA (The Albumin Website, 2018; Caridi et al, 2019)
These findings seem to indicate that CAA is the result of widely scattered randomly occurring different molecular defects (Ruhoff et al, 2010)
Summary
Congenital analbuminemia (CAA; OMIM # 616000) is an autosomal recessive disorder. In homozygous or compound heterozygous persons the trait leads to the complete absence or to strongly decreased concentrations of serum albumin. Protein electrophoresis of serum samples (Figure 2) and immunochemistry techniques are wellsuited screening methods for the potential detection of CAA, the wide range of the measured ALB levels, the absence of clear clinical and biochemical evidence, and the fact that hypoalbuminemia can be caused by many, often more common, disorders represent major pitfalls in the early clinical diagnosis of CAA. We identified a total of 19 different ALB variants (Tables 2, 3), 5 of them already described (Table 3) and 14 new (Table 2) None of the latter were present in homozygous state, this fact and the low frequency of the heterozygous confirm that the CAA is a rare disorder. 1/244334d aVariants are ordered on the basis of their position in the albumin gene. bbp and codon numbering are according to HGVS rules and are based on the cDNA sequence NM_000477.6. cFor the protein changes subtract 24 from amino acid numbers to convert to starting at the Asp of mature albumin. dPublic Dataset gnomAD (version 2.0.2.). ePublic Dataset Bravo
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
