Congenital analbuminaemia: Molecular defects and biochemical and clinical aspects

Minchiotti, Lorenzo; Galliano, Monica; Caridi, Gianluca; Kragh‐Hansen, Ulrich; Peters, Theodore

doi:10.1016/j.bbagen.2013.04.019

Cited by 38 publications

(77 citation statements)

References 54 publications

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“…Although not the first report of mutations [2][3][4] in the albumin gene in this condition, this case highlights the clinical importance of analbuminaemia and the associated hypercholesterolaemia. Analbuminaemia is very rare (estimated prevalence approximately one per million) and is usually an autosomal recessive condition.…”

mentioning

confidence: 70%

“…Most are nonsense mutations or mutations affecting splicing and frameshift/ deletions. [2][3][4][5] Albumin is quantitatively the most important protein contributing to the plasma colloid osmotic pressure, thereby playing a key role in body fluid distribution. Albumin also acts to bind and transport many substances, for example, calcium, bilirubin and free fatty acids, with the albumin-bound fractions usually physiologically inactive.…”

mentioning

confidence: 99%

“…9,10 Other associated medical conditions with analbuminaemia include respiratory tract infections, hypercoagulability, cutaneous angiomata and osteoporosis. [2][3][4][5][6] At the other end of the clinical spectrum of severity, intrauterine death may occur with analbuminaemia, and in neonates the clinical course is far more severe, with marked oedema and even death, thus illustrating the major biological role albumin plays in the pre-and perinatal period. [11][12][13][14][15] In less severe presentations, the near-absence of serum albumin results in compensatory increases, e.g.…”

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confidence: 99%

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Analbuminaemia: clinical features and associated hypercholesterolaemia

Crook

2016

Ann Clin Biochem

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confidence: 70%

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confidence: 99%

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confidence: 99%

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Analbuminaemia: clinical features and associated hypercholesterolaemia

Crook

2016

Ann Clin Biochem

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“…These data are consistent with generalized hyperlipidemia and other changes reported for human analbuminemia. 1,26,[28][29][30][31][32][33] Despite these serum changes, both Alb -/-strains are healthy, maintaining normal body weights and breeding similarly to their Alb C/C parental strains. Gross examinations by necropsy of »8 wks mice from both Alb -/-strains were unremarkable, lacking overt differences compared with the background strains, B6 and Tg32.…”

Section: Blood Chemistry and Gross Histopathologymentioning

confidence: 99%

Albumin-deficient mouse models for studying metabolism of human albumin and pharmacokinetics of albumin-based drugs

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Christianson³

et al. 2015

mAbs

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(2015) Albumin-deficient mouse models for studying metabolism of human albumin and pharmacokinetics of albumin-based drugs, mAbs, 7:2, 344-351, DOI: 10.1080DOI: 10. /19420862.2015 To link to this article: https://doi.org/10. 1080/19420862.2015 Serum albumin is the major determinant of blood colloidal osmotic pressure acting as a depot and distributor of compounds including drugs. In humans, serum albumin exhibits an unusually long half-life mainly due to protection from catabolism by neonatal Fc receptor (FcRn)-mediated recycling. These properties make albumin an attractive courier of therapeutically-active compounds. However, pharmaceutical research and development of albumin-based therapeutics has been hampered by the lack of appropriate preclinical animal models. To overcome this, we developed and describe the first mouse with a genetic deficiency in albumin and its incorporation into an existing humanized FcRn mouse model, B6.Cg-Fcgrt tm1Dcr Tg(FCGRT)32Dcr/DcrJ (Tg32). Albumin-deficient strains (Alb -/-) were created by TALEN-mediated disruption of the albumin (Alb) gene directly in fertilized oocytes derived from Tg32 mice and its nontransgenic background control, C57BL/6J (B6). The resulting Alb -/-strains are analbuminemic but healthy. Intravenous administration of human albumin to Tg32-Alb -/-mFcRn -/-hFcRn Tg/Tg ) mice results in a remarkably extended human albumin serum half-life of »24 days, comparable to that found in humans, and in contrast to half-lives of 2.6-5.8 d observed in B6, B6-Alb -/-and Tg32 strains. This striking increase can be explained by the absence of competing endogenous mouse albumin and the presence of an active human FcRn. These novel albumin-deficient models provide unique tools for investigating the biology and pathobiology of serum albumin and are a more appropriate rodent surrogates for evaluating human serum albumin pharmacokinetics and albumin-based compounds.

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“…2 The clinical diagnosis of CAA is based on serum protein electrophoresis, which shows a typical pattern: minimal ALB fraction (0.001-10 g/L) and variable compensatory increases in serum globulin concentrations. [3][4][5] The condition is characterized by surprisingly mild symptoms, such as mild oedema, hypotension, fatigue and, occasionally, a peculiar lower-body lipodystrophy, especially in adult females). [3][4][5] Hypercholesterolemia with elevated LDLcholesterol levels is a common finding, and some analbuminaemic individuals are treated with lipid-lowering drugs, although it is not clear whether premature atherosclerosis is present.…”

Section: Introductionmentioning

confidence: 99%

A novel splicing mutation in the albumin gene (c.270+1G>T) causes analbuminaemia in a German infant

et al. 2015

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Congenital analbuminaemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. The clinical diagnosis may be challenging because of the absence of unambiguous symptoms and because hypoalbuminemia may have many causes different from a genetic lack of the protein. We describe the clinical and molecular characterization of a new case of congenital analbuminaemia in an infant of apparently non-consanguineous parents from Treves, Germany. For molecular diagnosis, we used our strategy, based on the screening of the albumin gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing, which revealed that the proband is homozygous and both parents are heterozygous, for a novel G > T transversion at nucleotide c.270+ 1, the first base of intron 3. The mutation inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. In conclusion, we report the clinical findings and the molecular defect of this case, which contributes to a better understanding of the biological mechanism of congenital analbuminaemia.

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Congenital analbuminaemia: Molecular defects and biochemical and clinical aspects

Cited by 38 publications

References 54 publications

Analbuminaemia: clinical features and associated hypercholesterolaemia

Analbuminaemia: clinical features and associated hypercholesterolaemia

Albumin-deficient mouse models for studying metabolism of human albumin and pharmacokinetics of albumin-based drugs

A novel splicing mutation in the albumin gene (c.270+1G>T) causes analbuminaemia in a German infant

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