Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Department of Pathology and Laboratory Medicine; Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
J Clin Lipidol. 2022 Mar-Apr;16(2):155-159. doi: 10.1016/j.jacl.2022.02.003. Epub 2022 Feb 12.
Complete deficiency of apolipoprotein (apo) B-containing lipoproteins can result from both abetalipoproteinemia (ABL) and homozygous hypobetalipoproteinemia (HoHBL), caused by bi-allelic loss-of-function variants in the MTTP and APOB genes encoding microsomal triglyceride transfer protein and apolipoprotein (apo) B, respectively. Both conditions are associated with failure to assemble and secrete apo B-containing lipoproteins from intestine and liver, resulting in absence of chylomicrons, very low-density lipoproteins and remnants, and low-density lipoproteins. Because absorption and transport of fat soluble vitamins requires intact production of apo B-containing lipoproteins, untreated patients develop fat soluble vitamin deficiencies, with associated clinical features including atypical retinitis pigmentosa, osteopenia, neuromyopathy and coagulopathy. Other features include acanthocytosis on the peripheral blood film, fat malabsorption and hepatosteatosis. We describe two patients with ABL and one with HoHBL who have each been on high dose oral fat soluble vitamin replacement under the care of the same physician for more than four decades. Each patient has remained clinically stable. A recent liver biopsy from an ABL patient showed mild macrovesicular steatosis, patchy microvesicular steatosis and mild fibrosis. These observations add to our understanding of the long term trajectory of ABL and HoHBL, and emphasize the importance of compliance to treatment and follow up.
载脂蛋白（apo）B 所含脂蛋白完全缺乏可由两种情况引起：①贝特脂蛋白血症（ABL），由编码微粒体甘油三酯转移蛋白的 MTTP 基因和编码载脂蛋白（apo）B 的 APOB 基因的双等位基因功能丧失变异引起；②纯合性低β脂蛋白血症（HoHBL）。这两种情况均与肠和肝内载脂蛋白 B 所含脂蛋白的组装和分泌失败有关，导致乳糜微粒、极低密度脂蛋白和残粒以及低密度脂蛋白缺失。由于脂溶性维生素的吸收和转运需要完整的载脂蛋白 B 所含脂蛋白的生成，未经治疗的患者会发生脂溶性维生素缺乏，伴有特征性的临床表现，包括非典型性视网膜色素变性、骨质疏松、神经肌肉病和凝血功能障碍。其他特征包括外周血片上的棘状红细胞、脂肪吸收不良和肝脂肪变性。我们描述了 3 例 ABL 和 1 例 HoHBL 患者，他们均在同一位医生的治疗下接受了超过 40 年的高剂量口服脂溶性维生素替代治疗。每位患者的临床状况都保持稳定。一位 ABL 患者的最近一次肝活检显示轻度大泡性脂肪变性、局灶性微泡性脂肪变性和轻度纤维化。这些观察结果增加了我们对 ABL 和 HoHBL 长期病程的认识，并强调了遵医嘱治疗和随访的重要性。
