A case of lipoprotein glomerulopathy with a rare apolipoprotein E isoform combined with neurofibromatosis type I

Abstract

Lipoprotein glomerulopathy (LPG) is a rare inherited disease characterized by histopathological features of lipoprotein thrombi in dilated glomerular capillaries and type III like hyperlipoproteinemia with heterozygous mutation of the apolipoprotein (apo) E gene. We herein present the case of a 50-year-old woman with LPG complicated by neurofibromatosis type 1 (NF1). To the best of our knowledge, this is the first report of a case of LPG complicated by NF1. On the other hand, she had not only a heterozygous apoE-Sendai mutation, which is one of the most frequent apoE variants in LPG patients, but also a rare isoform of ApoE5 (Glu3Lys). Although apoE mutation has been recognized as having a principal role in the pathogenesis of LPG, some other factors are assumed to be present in the pathogenesis of LPG, because many asymptomatic carriers of apoE variants are recognized. The coexistence of NF1 or apoE5 (Glu3Lys) allele might play a role as an additional factor in the development of LPG.

Focal segmental glomerulosclerosis with heterozygous apolipoprotein E5 (Glu3Lys)

“…To explain this paradox, it is hypothesized that the enhanced metabolism of apoE5-containing lipoproteins results in hyperlipoproteinemia via the down-regulation of LDL receptors [2,3]; however, the precise mechanism is still unclear. A few cases of LPG associated with apoE5 (Glu3Lys) have been reported, but apoE variants specific to LPG, e.g., apoE-Chicago [4] and apoE-Sendai [5], were also detected in these cases, and the specific role of apoE (Glu3Lys) is unknown.…”

“…Since the serum apoE level exceeded the normal range, apoE phenotypes were analyzed by isoelectric focusing polyacrylamide gel electrophoresis, as previously described [4,5]. Different from apoE3/3 (a wild-type control), the apoE3/5 phenotype was detected in the patient (Fig.…”

“…Hyperlipidemic kidney disease is related to apoE5, and several cases of lipoprotein glomerulopathy (LPG) have recently been reported. However, other mutations specific to LPG, such as apoE-Chicago [4] and apoE-Sendai [5], have been detected in these cases and therefore the causative role of apoE5 is not clear.…”

Apolipoprotein E–related glomerular disorders

“…Additonally, apoE Chicago was also identified in a re-analysis 88 of the case previously analyzed by Miyata et al. 87 Takasaki et al 89 also reported a case of LPG with a combination of apoE Sendai and apoE5 (Glu3Lys). Thus, the occurrence of LPG cases with heterozygous apo E5 appears to be increasing, and all of these cases exhibit hypertriglyceridemia of $400 mg/dl.…”

“…Thus, the occurrence of LPG cases with heterozygous apo E5 appears to be increasing, and all of these cases exhibit hypertriglyceridemia of $400 mg/dl. 59,88,89 It is unknown if apoE5 plays a pathogenetic role in LPG, as apoE5 in these cases has always been associated with LPG-specific mutants such as apoE Chicago or apoE Sendai. Hypertriglyceridemia resulting from apoE5, however, is likely to be the trigger for LPG.…”