Anderson's disease/chylomicron retention disease in a Japanese patient with uniparental disomy 7 and a normal SAR1B gene protein coding sequence

Abstract

BackgroundAnderson's Disease (AD)/Chylomicron Retention Disease (CMRD) is a rare hereditary hypocholesterolemic disorder characterized by a malabsorption syndrome with steatorrhea, failure to thrive and the absence of chylomicrons and apolipoprotein B48 post-prandially. All patients studied to date exhibit a mutation in the SAR1B gene, which codes for an essential component of the vesicular coat protein complex II (COPII) necessary for endoplasmic reticulum to Golgi transport. We describe here a patient with AD/CMRD, a normal SAR1B gene protein coding sequence and maternal uniparental disomy of chromosome 7 (matUPD7).Methods and ResultsThe patient, one of two siblings of a Japanese family, had diarrhea and steatorrhea beginning at five months of age. There was a white duodenal mucosa upon endoscopy. Light and electron microscopy showed that the intestinal villi were normal but that they had lipid laden enterocytes containing accumulations of lipid droplets in the cytoplasm and lipoprotein-size particles in membrane bound structures. Although there were decreased amounts in plasma of total- and low-density lipoprotein cholesterol, apolipoproteins AI and B and vitamin E levels, the triglycerides were normal, typical of AD/CMRD. The presence of low density lipoproteins and apolipoprotein B in the plasma, although in decreased amounts, ruled out abetalipoproteinemia. The parents were asymptomatic with normal plasma cholesterol levels suggesting a recessive disorder and ruling out familial hypobetalipoproteinemia. Sequencing of genomic DNA showed that the 8 exons of the SAR1B gene were normal. Whole genome SNP analysis and karyotyping revealed matUPD7 with a normal karyotype. In contrast to other cases of AD/CMRD which have shown catch-up growth following vitamin supplementation and a fat restricted diet, our patient exhibits continued growth delay and other aspects of the matUPD7 and Silver-Russell Syndrome phenotypes.ConclusionsThis patient with AD/CMRD has a normal SAR1B gene protein coding sequence which suggests that factors other than the SAR1B protein may be crucial for chylomicron secretion. Further, this patient exhibits matUPD7 with regions of homozygosity which might be useful for elucidating the molecular basis of the defect(s) in this individual. The results provide novel insights into the relation between phenotype and genotype in these diseases and for the mechanisms of secretion in the intestine.

CideB Protein Is Required for the Biogenesis of Very Low Density Lipoprotein (VLDL) Transport Vesicle

“…Sar1, a COPII component that initiates vesicle biogenesis, has two mammalian homologs: Sar1a and Sar1b (31). Several studies have shown that Sar1b is involved in lipoprotein trafficking and secretion because mutations in Sar1b lead to chylomicron retention disease (32)(33)(34)(35)(36). The definitive role of Sar1 in VLDL exit from the hepatic ER has been evident from our data and those of others (15,21).…”

Analysis of copy number variations by SNP50 BeadChip array in Chinese sheep

“…The meat quality of foreign sheep is higher than that of domestic Chinese sheep, and Gansu Alpine Merino [40], and are also superior to some non-domestic breeds of sheep [41].…”

Recent discoveries on absorption of dietary fat: Presence, synthesis, and metabolism of cytoplasmic lipid droplets within enterocytes

“…Chylomicron retention disease (Anderson’s disease) [24] and abetalipoproteinemia [25, 26] are two examples of diseases where CM synthesis or secretion are inhibited and TAG accumulates in CLDs within enterocytes, ultimately resulting in fat malabsorption or steatorrhea due to enterocyte turnover. Pluronic L81 (PL81) is a surfactant that has been investigated because of its beneficial effects on reducing blood TAG and cholesterol levels.…”