Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
J Clin Lipidol. 2018 Jul-Aug;12(4):878-882. doi: 10.1016/j.jacl.2018.04.005. Epub 2018 Apr 21.
Low high-density lipoprotein cholesterol (HDL-C) can be caused by several acquired secondary causes as well as primary genetic disorders. However, only a few conditions are associated with profoundly reduced levels below 10 mg/dL. We present an unusual case of a healthy man with severely decreased HDL-C because of a novel homozygous variant causing a Proline > Arginine amino acid change at position 1412 in the ATP-binding cassette transporter A1 gene. Homozygous variations in ATP-binding cassette transporter A1 typically cause Tangier disease, a rare autosomal recessive condition linked with several other abnormalities (eg, enlarged discolored tonsils). Despite having an HDL-C below 10 mg/dL, our patient presented without any other clinical symptoms or physical signs suggestive of Tangier disease. This case of presumptive Tangier disease adds support to the growing body of evidence that this genetic disorder may have greater phenotypic heterogeneity along with a more varied presentation than traditionally considered.
低高密度脂蛋白胆固醇（HDL-C）可由多种后天性继发原因和原发性遗传疾病引起。然而，只有少数情况与极低的水平（低于 10mg/dL）相关。我们报告了一例罕见的因新的纯合变异导致 ATP 结合盒转运体 A1 基因第 1412 位脯氨酸突变为精氨酸的纯合子变异而致 HDL-C 严重降低的健康男性病例。ATP 结合盒转运体 A1 的纯合子变异通常导致 Tangier 病，这是一种罕见的常染色体隐性遗传疾病，与其他几种异常相关（例如，扁桃体增大和变色）。尽管我们的患者 HDL-C 低于 10mg/dL，但他没有出现任何其他临床症状或体征提示 Tangier 病。本例疑似 Tangier 病增加了越来越多的证据支持，即这种遗传疾病可能比传统上认为的具有更大的表型异质性和更多样的表现。
