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Severe hypercholesterolemia in a patient with very low albumin and normal renal function

Published:November 09, 2022DOI:https://doi.org/10.1016/j.jacl.2022.10.011

      Highlights

      • Very low albumin levels are associated with hypercholesterolemia.
      • Congenital analbuminemia (CAA) is a rare cause of hyperlipidemia.
      • CAA is established by genetic testing of ALB.
      • Early diagnosis may enable earlier lipid therapy to prevent coronary artery disease.
      • This is the first report of PCSK9 inhibitor for hyperlipidemia associated with CAA.
      A 20-year-old male presented with severe elevation in low-density lipoprotein cholesterol (LDL-C). Initial genetic testing for familial hypercholesterolemia was negative. Patient also had low albumin, and further genetic testing showed homozygous variants in the ALB gene, suggesting congenital analbuminemia (CAA) causing severe hyperlipidemia. CAA is an autosomal recessive disorder with incidence of about 1:1,000,000. The gene for albumin is a single autosomal gene, and pathological variants that affect splicing lead to premature stop, nonsense variants, and deletions that result in a defect in albumin synthesis with CAA. CAA can be fatal in the prenatal period and cause infections in early childhood. CAA is tolerated better in adulthood because of compensatory increase in other plasma proteins. Plasma lipoproteins also increase, and CAA can cause gross hyperlipidemia with severe elevations in LDL-C and hypercholesterolemia. Genetic examination of ALB is mandatory to establish the diagnosis. Early diagnosis may be important to initiate lipid-lowering treatments to avoid premature coronary artery disease.

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