Impaired lipid transport due to heterozygous hypobetalipoproteinemia.

Objectives: The aims of the study were to evaluate lipidic pattern and clinical phenotype in patients affected by familial hypo-lipoproteinemia (FHBL), and to investigate the genetic basis of the disease. Methods: Subjects were recruited in the study for the presence of abnormally low total cholesterol levels in plasma (<5th percentile). Every patient was submitted to clinical and laboratory tests to rule out secondary hypocholesterolemia and to check the presence and the nature of disease’s typical clinical manifestations. Lipoprotein profile was performed on every subject. In one case the diagnosis was established by genetic investigation. Results: 10 out of 21 tested subjects, were affected by heterozygous FHBL; 3 of these patients were in pediatric age. In 6 cases hepatic echotomography revealed fatty liver; hepatic cirrhosis was present in one case. The genetic investigation, in one patient, revealed a not previously described mutation of the apoprotein B (apoB) gene, resulting in a premature stop codon; the truncated apoprotein synthesized from this gene was named apoB 32,4. The same subject reported symptoms of fat malabsorption. Conclusions: Signs and symptoms in these FHBL subjects most likely results from the reduced synthesis of truncated B apoproteins and from the inability of these apoBs to export lipids from cells into the blood stream. Heterozygous FHBL should be considered in all hypolipidemic subjects, in absence of diseases generating secondary hypocholesterolemia.