Peretti Noel, Roy Claude C, Sassolas Agnès, Deslandres Colette, Drouin Eric, Rasquin Andrée, Seidman Ernest, Brochu Pierre, Vohl Marie-Claude, Labarge Sylvie, Bouvier Raymonde, Samson-Bouma Marie-Elizabeth, Charcosset Mathilde, Lachaux Alain, Levy Emile
Department of Nutrition, CHU Sainte-Justine, Université de Montréal, GI-Nutrition Unit, 3175 Ste-Catherine Road, Montreal, Que., Canada.
Mol Genet Metab. 2009 Jun;97(2):136-42. doi: 10.1016/j.ymgme.2009.02.003. Epub 2009 Feb 20.
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 (X age 11.3+/-1.7 years) and 9 from Quebec, Canada (X age 12+/-2.5 years) 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.
脂蛋白组装对于膳食脂质和脂溶性维生素的肠道吸收至关重要。编码Sar1 GTP酶的Sar1B基因突变通过抑制乳糜微粒分泌，与乳糜微粒滞留病（CRD）相关。本研究的目的是描述两个临床和基因特征明确的队列中CRD的表型表达，并比较它们的长期演变。对来自法国的7名儿童（平均年龄11.3±1.7岁）和来自加拿大魁北克的9名儿童（平均年龄12±2.5岁）的研究，涉及从病历中收集生长评估、神经和眼科状况以及骨密度的数据，法国队列的平均随访期为4.9年，加拿大队列为10.6年。所有CRD患者在出生后的头几个月内出现腹泻和发育不良。严重低胆固醇血症伴甘油三酯正常与低密度脂蛋白和高密度脂蛋白胆固醇降低以及载脂蛋白A-I和B降低有关。观察到不同程度的必需脂肪酸和维生素E缺乏。加拿大队列（1.3±0.04岁）比法国队列（6.3±1.3岁）的诊断更早，但与出现症状的严重程度无关。在后一组中疾病对生长和骨密度的影响更大这一事实可能与疾病诊断延迟有关。维生素E缺乏在少数患者中导致功能性神经和眼科改变，但只有1例出现无反射。最后，在我们的CRD队列中基因型与表型的相关性不明显；即使携带409G>A等位基因的加拿大受试者的低胆固醇血症程度比其他患者更严重（P<0.001），许多临床数据也与假设的基因型-表型相关性不一致。这项研究为CRD随时间的表型表达提供了新的见解，并强调有必要对慢性腹泻和发育不良的婴儿进行血脂筛查。
