Abetalipoproteinemia: two case reports and literature review

Abstract

Abetalipoproteinemia (ABL, OMIM 200100) is a rare, autosomal recessive disorder, characterized by fat malabsorption, acanthocytosis and hypocholesterolemia in infancy. Later in life, deficiency of fat-soluble vitamins is associated with development of atypical retinitis pigmentosa, coagulopathy, posterior column neuropathy and myopathy. ABL results from mutations in the gene encoding the large subunit of microsomal triglyceride transfer protein (MTP; OMIM 157147). To date at least 33 MTP mutations have been identified in 43 ABL patients. We describe the clinical progress of two patients, both currently in the fifth decade of life, who were diagnosed with ABL as children and were treated with high oral doses of fat soluble vitamins, including vitamin E over the last three decades. Treatment appears to have been associated with arrest of the neuropathy and other complications in both patients. Because pharmacologic inhibition of MTP is being developed as a novel approach to reduce plasma cholesterol for prevention of cardiovascular disease, defining the long-term clinical features of patients with a natural deficiency in MTP might provide some insight into the possible effects of such treatments. We review the range of clinical, biochemical and molecular perturbations in ABL.

Figure 1

Acanthocytes on the peripheral blood smear of case #1.

Figure 2

Genetic map of MTP mutations in patients with abetalipoproteinemia. The map shows the genomic structure of MTP gene. Black boxes represent exons; dotted lines point to mutation positions. Above the map are single-nucleotide and small insertion-deletion mutations. Nucleotide position in reference to the first ATG of MTP cDNA (GenBank Accession No. NM_000253) are shown. Directly under the linear map are splicing mutations. The position relative to the intron-exon boundary is shown numerically. Larger deletions are shown as horizontal lines below the linear map, with the span of the deleted region indicated by text label.