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Congenital analbuminemia (CAA) is characterized by the absence or dramatic reduction of circulating human serum albumin (HSA).
- Synonym(s): -
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: R77.0
- OMIM: 616000
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
Prevalence has been estimated at approximately 1 case per million population, with less than 50 cases being reported in the literature so far. The disorder occurs with no geographic, sex or ethnic predilection.
In the majority of cases, CAA is diagnosed in adulthood. Although albumin is the most abundant plasma protein and has many functions, patients with CAA present with only a few mild clinical signs and biochemical abnormalities: fatigue, low blood pressure, edema, increased concentration of several plasma proteins and a prolonged albumin half-life. HSA is either absent or present at very low levels (<1 g/L) but liver function is normal and there is an absence of conditions leading to significant protein loss. The mildness of the clinical manifestations is attributed to the compensatory increase in hepatic biosynthesis of other plasma proteins, notably a compensatory increase in serum globulin concentrations. However, CAA patients may develop lipodystrophy and hypercholesterolemia, possibly leading to premature atherosclerosis and cardiovascular events. Rarely, CAA may be complicated by hypercoagulability, osteoporosis and respiratory tract infections. The disorder appears to be more severe in the fetus or during early infancy, as intrauterine growth retardation and intrauterine death have been reported.
The disorder is caused by homozygous or compound heterozygous mutations in the gene coding for HSA (ALB; 4q13.3). More than ten different causative mutations have been identified to date. The Kayseri mutation (a homozygous AT deletion at nucleotides c.228-229, the 91st and 92nd bases of exon 3) appears to be the most common cause of analbuminemia in humans.
Diagnosis is based on laboratory analysis of blood specimens (albumin immunoassays and serum protein electrophoresis). DNA analysis is required for identification of the mutation involved.
The differential diagnosis should include a wide number of pathological conditions that present with reduction of HSA (glomerulonephritis, nephrosis, ascites, systemic lupus erythematosus, intestinal lymphangiectasia, and protein-losing enteropathies; see these terms).
CAA is transmitted as an autosomal recessive trait and consanguinity has been shown in all reported cases with available genealogic data.
Management and treatment
CAA is a relatively benign and tolerable condition. Management aims at prophylaxis and treatment of the possible cardiovascular complications related to hypercholesterolemia and atherosclerosis. Drugs that bind to the albumin plasma protein fraction should be used with caution in patients with CAA.