Tangier Disease

We describe two patients with Tangier disease (TD) and provide a narrative review of its clinical features, genetics, diagnosis, and management. A literature search of PubMed and Google Scholar was performed to identify English-language publications on TD, and relevant articles were reviewed narratively.

Patient # 1 was diagnosed with TD due to compound heterozygous variant in ABCA1 (one pathogenic variant (c.1759 C > T, p.Arg587Trp) and one variant of uncertain significance (VUS) (c.1733 C > G, p.Pro578Arg)) when evaluated for histopathological findings of tonsillectomy specimen suggestive of TD. Patient # 2 was found to have TD due to homozygous pathogenic variant in ABCA1 (c.1769G > T p. Trp590Leu) when evaluated for incidental detection of low high density lipoprotein (HDL-C). TD, characterized by HDL-C deficiency affects reverse cholesterol transport causing intracellular cholesterol accumulation in various tissues producing characteristic clinical presentation. There is no definite treatment for TD. To the best of our knowledge the VUS noted in patient # 1 is likely pathogenic. This report will aid a variant reclassification.