Abetalipoproteinemia With a Novel Microsomal Triglyceride Transfer Protein Gene Mutation and Unique Oxidized...

Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by pathogenic variants in the microsomal triglyceride transfer protein (MTTP) gene, resulting in the defective secretion of apolipoprotein B (APOB)-containing lipoproteins. Although ABL can theoretically have a low risk of cardiovascular disease (CVD) due to the defective secretion of APOB-containing lipoproteins, the previously reported cases of ABL are limited and its CVD-related pathophysiology thus remains unestablished. We encountered a 25-year-old male patient with very low levels of lipids and lipoproteins. In addition to observing his signs and symptoms, we assayed serum oxidized forms of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles using an enzyme-linked immunosorbent assay (ELISA). Variants in the APOB and MTTP genes were analyzed using next-generation sequencing (NGS). As a result, the patient exhibited low levels of total cholesterol (TC), triglycerides (TGs), LDL-cholesterol, and HDL-cholesterol. The oxidized LDL level was measured under a detectable limit, while oxidized HDL showed a relatively high level. An in-frame deletion in MTTP (p.Ser615del), a novel type of gene mutation, was identified in a homozygous manner. The patient had no obvious signs or symptoms of fat malabsorption or any neurological manifestations. In summary, we described a case of ABL with a novel MTTP mutation, p.Ser615del, without typical signs or symptoms. There were markedly low levels of atherogenic lipids and oxidized LDL, while the relatively high level of oxidized HDL with the low level of HDL-cholesterol appeared, which might offer unique insights into the pathophysiology of CVD-related risk in ABL. Further data accumulation of ABL is expected to clarify the disease picture.