Chylomicron retention disease: A long term study of two cohorts

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• 作者：Noel Peretti ; Claude C. Roy ; Agnè ; s Sassolas ; Colette Desl ; res ; Eric Drouin ; André ; e Rasquin ; Ernest Seidman ; Pierre Brochu ; Marie-Claude Vohl ; Sylvie Labarge ; Raymonde Bouvier ; Marie-Elizabet
• 关键词：Sar1B gene mutations ; Fatty acid composition ; Cholesterol ; Apolipoproteins ; Liposoluble vitamins
• 刊名：Molecular Genetics and Metabolism
• 出版年：2009
• 出版时间：June 2009
• 年：2009
• 卷：97
• 期：2
• 页码：136-142
• 全文大小：227 K

文摘

Lipoprotein assembly is critical for the intestinal absorption of dietary lipids and of fat-soluble vitamins. Through their inhibition of chylomicron secretion, mutations of the Sar1B gene coding for Sar1 GTPase are associated with chylomicron retention disease (CRD). The aim of this study was to describe the phenotypic expression of CRD in two clinically and genetically well characterized cohorts, and to compare their long term evolution. The study in 7 children from France ( age 11.3 ± 1.7years) and 9 from Quebec, Canada ( age 12 ± 2.5years) involved data collection from medical records for growth evaluation, neurological and ophthalmological status as well as bone density over an average follow-up period of 4.9 years for the French cohort and of 10.6 years for the Canadian one. All CRD patients presented within the first few months of life with diarrhea and failure to thrive. Severe hypocholesterolemia coupled with normal triglycerides was associated with low LDL and HDL-cholesterol, as well as with low apolipoproteins A-I and B. Varying degrees of essential fatty acid and of vitamin E deficiency were observed. The earlier diagnosis in the Canadian cohort (1.3 ± 0.04 years) than in the French one (6.3 ± 1.3 years) was unrelated with the severity of presenting symptoms. The fact that the disease had more impact on growth and bone density in the latter group may be related to delayed diagnosis of the disease. Vitamin E deficiency led to functional neurological and ophthalmic changes in a small number of patients but only one developed areflexia. Finally, genotype–phenotype correlation is not obvious in our cohort with CRD; even if, the Canadian subjects with the allele 409G>A had a more severe degree (P < 0.001) of hypocholesterolemia than the other patients, many clinical data are inconsistent with a hypothetical genotype–phenotype correlation. This study provides new insights on the phenotypic expression of CRD over time and emphasizes the need to screen the lipid profile of infants with chronic diarrhea and failure to thrive.