Key result
Pathogenic ABCA1 variants cause classic Tangier disease with near-absent HDL-C in pediatric patients.
Why the study?
Tangier disease is a rare HDL-C deficiency disorder with limited clinical characterization and no definite treatment, necessitating detailed case descriptions and genetic analysis.
Case Report (n=2)
This narrative review and case series highlights the phenotypic variability of Tangier disease, presents a novel ABCA1 variant likely to be pathogenic, and underscores the importance of integrating clinical, biochemical, and genetic data for diagnosis.
Answers are grounded in this paper and cite their sources.
Supports genetic evaluation for Tangier disease in children with very low HDL-C; extends ABCA1 variant spectrum in pediatric cases.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.
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Pillai et al. (2026) conducted a case report in Tangier disease (n=2). ABCA1 pathogenic variants was evaluated. Compound heterozygous and homozygous pathogenic variants in the ABCA1 gene were identified in two male pediatric patients presenting with classic features of Tangier disease and near-absent HDL cholesterol.
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