Extreme Contrast of Postprandial Remnant-Like Particles Formed in Abetalipoproteinemia and Homozygous Familial Hypobetalipoproteinemia

Abstract

Background: Familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL) are rare inherited forms of hypolipidemia. Their differential diagnosis is important for predicting of the prognosis and selecting appropriate therapy.Materials and Methods: Genetic analysis was performed in two patients with primary hypocholesterolemia born from consanguineous parents. The oral fat tolerance test (OFTT) was performed in one patient with FHBL (apoB-87.77) and one with ABL as well as in four normal control subjects. After overnight fasting, blood samples were drawn. Serum lipoprotein and remnant-like particle (RLP) fractions were determined by HPLC analysis.Results: Both patients with homozygous FHBL were asymptomatic probably because of preserved levels of fatsoluble vitamins, especially vitamin E. The patients with FHBL were homozygous because of novel apoB-83.52 and apoB-87.77 mutations, and although one of them (apoB-87.77) had fatty liver disease, microscopic findings suggesting nonalcoholic steatohepatitis were absent. Fasting apoB-48 and RLP-triglyceride levels in the patient with homozygous FHBL, which were similar to those in normal control subjects, increased after OFTT both in normal control subjects and the patient with FHBL but not in the patient with ABL, suggesting that the fat load administered was absorbed only in the patient with FHBL.Conclusion: Although lipid levels in the patients with homozygous FHBL and ABL were comparable, fasting, postoral fat loading of apoB-48, as well as RLP-triglyceride

Encouragement of Super-aggressive LDL-lowering Therapies

“…3), although he suffers from spinocerebellar ataxia, and retinal pigmentary degeneration due to lack of fat-soluble vitamin 14) . On the contrary, we have shown an interesting case of homozygous familial hypobetalipoproteinemia (FHBL) whose LDL-C was as low as 1 mg/dl 15) . He does not exhibit any complications relating fat-soluble vitamin deficiency…”

Low-Density Lipoprotein Cholesterol Level cannot be too Low: Considerations from Clinical Trials, Human Genetics, and Biology

“…2), although he suffers from spinocerebellar ataxia, and retinal pigmentary degeneration due to lack of fat-soluble vitamin 17) . On the contrary, we have shown an interesting case of homozygous familial hypobetalipoproteinemia (FHBL) whose LDL cholesterol was as low as 1 mg/dl 18) . The patient did not exhibit any complications relating to fat-soluble vita-standard care (mean LDL cholesterol level was 104.1 mg/dl).…”

“…2 ) , although he suffers from spinocerebellar ataxia, and retinal pigmentary degeneration due to lack of fat-soluble vitamin 17 ) . On the contrary, we have shown an interesting case of homozygous familial hypobetalipoproteinemia (FHBL) whose LDL cholesterol was as low as 1 mg/dl 18 ) . The patient did not exhibit any complications relating to fat-soluble vitamin deficiency, as described above, probably due to his preserved HDL cholesterol (HDL cholesterol ∼60 mg/dl) level containing fat-soluble vitamins It would be important to see that none of the family members whose LDL cholesterol was quite low had atherosclerotic diseases.…”

Current Diagnosis and Management of Abetalipoproteinemia

“…Catabolism of HDL, particularly apoE-containing HDL, may be increased, contributing to the apparently normal delivery of cholesterol to peripheral tissues in the absence of apoB-containing lipoproteins in ABL patients 7) . Plasma TG levels in ABL are typically less than 10 mg/ dL 7) and do not increase after a dietary fat load 2,7,48) . Although the levels of TC and TG are variable in ABL patients, plasma levels of low-density lipoprotein (LDL) and apoB are consistently absent or extremely low.…”