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

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.