Response to therapy of a type III hyperlipoproteinemic subject with the rare apolipoprotein E1 (Gly127 ? Asp, Arg158 ? Cys) variant

Abstract

In a preceding paper, we described the molecular biological defects in a patient with a severe form of the familial lipoprotein disorder type III hyperlipoproteinemia (HLP) and an unusual apolipoprotein (apo) E1 phenotype and epsilon 1/"null" genotype. The index case was a 60-year-old white male of German ancestry who suffered from a myocardial infarction at age 50 years. He had distinctly elevated levels of plasma lipids (triglycerides 551 mg/dl and cholesterol 747 mg/dl, respectively) and typical clinical signs of this inborn error of lipoprotein metabolism. His mutant apo E1 was shown to be identical to a rare (already described) apo E1 (Gly127----Asp, Arg158----Cys) variant. A second independent defect at the molecular level was a nucleotide deletion of a guanosine (G) in the codon for amino acid 31 of the proband's apo epsilon 3 allele. This single base deletion (not described before) changed his apo epsilon 3 allele to a nonfunctional "null" allele devoid of a stable gene product. Here we describe the response to combined dietary and medical treatment of the patient with this unusual form of type III HLP. His response to therapy was excellent, similar to patients with "classical" type III HLP and homozygosity for apo E2. However, the correct diagnosis of this familial lipoprotein disorder seems to be necessary, even in patients without the expected apo E2/2 phenotype, in terms of the prompt and beneficial response to therapeutic interventions.