Analbuminemia: three cases resulting from different point mutations in the albumin gene.

Abstract

Analbuminemia is a very rare recessive disorder in which subjects have little or no circulating albumin, although albumin is normally the most abundant plasma protein and has many functions. Analbuminemla is caused by a variety of mutations in the albumin gene and is exhibited only by subjects homozygous for the defect. Previously the mutation had been identified at the molecular level in only two human cases; in one case it resulted from an exon-splicing defect, and in the other case it was caused by a nucleotide insertion that caused a frameshift and premature stop codon. In this investigation we identified the mutations in three unrelated subjects from different countries. In each instance a single-nucleotide mutation produced a stop codon, but the mutations occurred at three different sites: (i) in an Italian male a C -> T transition at nt 2368 in the genomic sequence of albumin, (u) a C -. T transition at nt 4446 for an American female, and (iU) a G -+ A transition at nt 7708 in a Canadian male. The size of the albumin fragment that might have been produced for the three cases varied from 31-to 213-amino acid residues, but no evidence for a circulating albumin fragment was obtained. The paradox is that analbuminea is extremely rare (frequency <

A boy with congenital analbuminemia and steroid-sensitive idiopathic nephrotic syndrome: an experiment of nature

“…A few publications have reviewed the clinical presentation and long-term outcome of patients with CAA [8,9,12,16,21]. However, follow-up data are incomplete and inconsistent in some cases.…”

“…However, follow-up data are incomplete and inconsistent in some cases. Thus, despite the very high serum concentrations of total and LDL cholesterol, the risk of progressive atherosclerosis and cardiovascular events is still not well defined; yet, an increased risk of atherosclerosis cannot be excluded [8,9,12,16,21]. Well documented complications were lipodystrophy (mainly in adult females) and osteoporosis.…”

“…CAA is a rare autosomal recessive disorder [4,9,18,21] leading to defective albumin synthesis in the liver [23] with subsequent very low serum albumin concentration (<0.2 g/dl). If albumin is administered intravenously to patients with CAA, its biologic half-life is prolonged to 38 -50 days (reference range: 16 -20 days) [21,23]; on the contrary, the half-life in our patients was very short (<5 days), raising the question of albuminuria.…”

“…Marked edema, however, is absent, and only half of these patients present with mild peripheral edema, indicating the presence of edema-preventive measures [reviewed in 12,16]. Increased concentrations of nonalbumin proteins (mainly alpha 1, alpha 2 and beta globulins) [8,12,23] and lipoproteins [8,12,16,21], and lowering in parallel of the interstitial oncotic pressure through washout of interstitial colloids and increased lymph drainage, mitigate the effect on the capillary oncotic pressure and the transcapillary oncotic gradient [8,12,16]. In addition, there is a reduction of the hydrostatic pressure gradient by lowering the capillary blood pressure and increasing the interstitial pressure [14].…”

Perinatal and childhood morbidity and mortality in congenital analbuminemia

“…Previously reported CAA cases describe individuals as being relatively asymptomatic, with the most frequently associated complications including lipodystrophy, hypercholesterolemia, frequent lower respiratory tract infections (LRTI) in children and low birth weight (1). Few reports have provided antenatal and maternal history, although it has been hypothesized that the low incidence of CAA may in part be due to affected fetuses creating an inhospitable in-utero environment (1,2). CAA is a rare condition with 50 cases having been recorded since 1954, with an estimated frequency of 1 in 1,000,000 (3).…”