Case Study| Volume 17, ISSUE 1, P64-67, January 2023

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

Published:November 09, 2022DOI:


      • 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.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Clinical Lipidology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Arques S.
        Serum albumin and cardiovascular disease: state-of-the-art review.
        Ann Cardiol Angeiol (Paris). 2020; 69: 192-200
        • González-Pacheco H
        • Amezcua-Guerra LM
        • Sandoval J
        • et al.
        Prognostic implications of serum albumin levels in patients with acute coronary syndromes.
        Am J Cardiol. 2017; 119: 951-958
        • Kim S
        • McClave SA
        • Martindale RG
        • Miller KR
        • Hurt RT.
        Hypoalbuminemia and clinical outcomes: what is the mechanism behind the relationship?.
        Am Surg. 2017; 83: 1220-1227
        • Agrawal S
        • Zaritsky JJ
        • Fornoni A
        • Smoyer WE.
        Dyslipidaemia in nephrotic syndrome: mechanisms and treatment.
        Nat Rev Nephrol. 2018; 14: 57-70
      1. Online Mendelian Inheritance in Man, OMIM. MIM number: 616000: Analbuminemia; ANALBA. Accessed 11 May 2022.

        • Minchiotti L
        • Caridi G
        • Campagnoli M
        • Lugani F
        • Galliano M
        • Kragh-Hansen U.
        Diagnosis, phenotype, and molecular genetics of congenital analbuminemia.
        Front Genet. 2019; 10: 336
        • Caridi G
        • Lugani F
        • Angeletti A
        • Campagnoli M
        • Galliano M
        • Minchiotti L.
        Variations in the human serum albumin gene: molecular and functional aspects.
        Int J Mol Sci. 2022; 23: 1159
        • Toye JM
        • Lemire EG
        • Baerg KL.
        Perinatal and childhood morbidity and mortality in congenital analbuminemia.
        Paediatr Child Health. 2012; 17: e20-e23
        • Minchiotti L
        • Galliano M
        • Caridi G
        • Kragh-Hansen U
        • Peters T Jr.
        Congenital analbuminaemia: molecular defects and biochemical and clinical aspects.
        Biochim Biophys Acta. 2013; 1830: 5494-5502
        • Del Ben M
        • Burattin M
        • Arca M
        • Ceci F
        • Violi F
        • Angelico F
        Treatment of severe hypercholesterolemia with atorvastatin in congenital analbuminemia.
        Am J Med. 2004; 117: 803-804
        • Garoufi A
        • Koemtzidou E
        • Katsarou E
        • et al.
        Lipid profile and thyroid hormone concentrations in children with epilepsy treated with oxcarbazepine monotherapy: a prospective long-term study.
        Eur J Neurol. 2014; 21: 118-123
        • Enkhmaa B
        • Berglund L.
        Non-genetic influences on lipoprotein(a) concentrations.
        Atherosclerosis. 2022; 349: 53-62
        • Molina-Jijon E
        • Gambut S
        • Macé C
        • Avila-Casado C
        • Clement LC.
        Secretion of the epithelial sodium channel chaperone PCSK9 from the cortical collecting duct links sodium retention with hypercholesterolemia in nephrotic syndrome.
        Kidney Int. 2020; 98: 1449-1460
        • Demirsoy E
        • Sirin G
        • Ozker E.
        Coronary artery bypass surgery in a patient with analbuminemia.
        Tex Heart Inst J. 2011; 38: 85-87
        • Yeang C
        • Karwatowska-Prokopczuk E
        • Su F
        • et al.
        Effect of pelacarsen on lipoprotein(a) cholesterol and corrected low-density lipoprotein cholesterol.
        J Am Coll Cardiol. 2022; 79: 1035-1046