| Summary: | We describe here two patients, M. P. and S. L., with recessive abetalipoproteinemia. Analysis of restriction fragments of DNA from both patients using cDNA probes spanning the entire apolipoprotein B gene revealed no major insertions or deletions. Further, as defined by restriction fragment length polymorphism, abetalipoproteinemia, in these patients, did not appear associated with particular alleles of apolipoprotein B. Northern and dot blot analysis of intestinal mRNA of one patient (M. P.) revealed a normal-sized apolipoprotein B mRNA which was present in slightly reduced amounts. At the cellular level apolipoprotein B was detected in both intestinal and hepatic biopsies, of one patient (S. L.), by immunoenzymatic techniques using polyclonal and monoclonal antibodies to apolipoprotein B-48 and/or B-100. The level of apolipoprotein B-48 appeared to increase in the intestine after a fatty meal. In the other patient (M. P.), although no apolipoprotein B was detected in the enterocytes using similar immunoenzymatic techniques, organ culture experiments using [35S]methionine demonstrated the synthesis of a normal-sized apolipoprotein B-48 which appeared to be normally glycosylated. The glycosylation and processing of two intestinal membrane enzymes, sucrase-isomaltase and aminopeptidase N, were also normal. Although lipids and apolipoprotein B-48 were present intracellularly, no lipoprotein-like particles were observed by electron microscopy in the endoplasmic reticulum, the Golgi apparatus, or in the intercellular spaces of intestinal biopsies obtained in the fasted (M. P. and S. L.) or fed state (S. L.). The defect in these cases of abetalipoproteinemia, therefore, does not appear to involve the apolipoprotein B gene nor the synthesis or the glycosylation of the apolipoprotein but instead appears to involve some aspect of lipoprotein assembly or secretion.
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