The value and limitations of genetic testing in diagnosing and advising on cardiovascular risk in the rare Tangier Disease

Background: Dysfunctional variants in the ATP-binding cassette transporter A1 (ABCA1) gene cause the very rare and autosomal recessive Tangier disease.Classical clinical features include orange-coloured pharyngeal tonsils, hepatosplenomegaly and sensory neuropathy.Affected individuals have low levels of both HDL-cholesterol (HDL; <1 to 13% of normal) and apolipoprotein A1 (ApoA1).However, the autosomal dominant familial HDL deficiency (FHD) can also be caused by variant(s) in the ABCA1 gene and also presents with low levels of HDL (30 to 83% of normal) and ApoA1.The typical clinical presentation is of yellow/ brown xanthomata.Both conditions are associated with an increased risk of cardiovascular disease; with Tangier disease considered to carry a more significant risk.The conditions are thought to be related, where one ABCA1 variant is associated with FHD and two ABCA1 variants with Tangier disease. Case history: Adult female 65-year-old patient reviewed in the Lipid clinic. Steps to confirming a diagnosis;This article is part of a special issue entitled: Heart UK 2026