A novel variant in the ABCA1 gene for Tangier Disease with diffuse histiocytosis of bone marrow.

Abstract

Tangier disease is an extremely rare autosomal recessive monogenic disorder caused by mutations in the ATP binding cassette transporter A1 gene (ABCA1). It is characterized by severe deficiency or absence of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA1), with highly variable clinical presentations depending on cholesterol accumulation in macrophages across different tissues. We report a case of a 47-year-old man with very low HDL-C and very high triglyceride levels, initially attributed to the patient's metabolic syndrome, alcohol abuse, and splenomegaly. He had pancytopenia and splenomegaly for over fourteen years and developed premature myocardial infarction during his diagnostic workup. Suspecting of Tangier disease, we sequenced the ABCA1 gene, which revealed a homozygous new variant c.164A>G p (His5Arg) in the exon 4. Given the limited number of published cases, there are no reliable data on genotype-phenotype correlations in Tangier disease, highlighting the importance of reporting new variants and associated clinical features.