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Abstract：
BACKGROUND: Our aims were to describe the first Mexican patient with abetalipoproteinemia and to perform a comparative analysis of biochemical, clinical, and genetic characteristics of 100 cases reported in the literature.
METHODS: We performed biochemical and molecular screenings in a Mexican girl with extremely low lipid levels and in her family. Further, we integrated and evaluated the characteristics of the cases with abetalipoproteinemia described in the literature.
RESULTS: Our patient is a six-year-old girl who presented vomiting, chronic diarrhea, failure to thrive, malabsorption, acanthocytosis, anemia, transaminases elevation, and extremely low lipid levels. MTTP gene sequencing revealed homozygosity for a novel mutation p.Gly417Valfs*12 (G deletion c.1250). With the analysis of the reported cases, 60 clinical features (14 classical and 46 non-classical) were observed, being the most common acanthocytosis (57.5%), malabsorption (43.7%), and diarrhea (42.5%); 48.8% of the patients presented only classic clinical features, while the remaining 51.2% developed secondary effects due to a fat-soluble vitamin deficiency. An odds ratio analysis disclosed that patients diagnosed after 10 years of age have an increased risk for presenting clinical complications (OR = 18.0; 95% CI 6.0-54.1, p < 0.0001). A great diversity of mutations in MTTP has been observed (n = 76, being the most common p.G865X and p.N139_E140) and some of them with possible residual activity.
CONCLUSIONS: The first Mexican patient with abetalipoproteinemia presents a novel MTTP mutation p.Gly417Valfs*12. Three factors that could modulate the phenotype in abetalipoproteinemia were identified: age at diagnosis, treatment, and the causal mutation.
METHODS: We performed biochemical and molecular screenings in a Mexican girl with extremely low lipid levels and in her family. Further, we integrated and evaluated the characteristics of the cases with abetalipoproteinemia described in the literature.
RESULTS: Our patient is a six-year-old girl who presented vomiting, chronic diarrhea, failure to thrive, malabsorption, acanthocytosis, anemia, transaminases elevation, and extremely low lipid levels. MTTP gene sequencing revealed homozygosity for a novel mutation p.Gly417Valfs*12 (G deletion c.1250). With the analysis of the reported cases, 60 clinical features (14 classical and 46 non-classical) were observed, being the most common acanthocytosis (57.5%), malabsorption (43.7%), and diarrhea (42.5%); 48.8% of the patients presented only classic clinical features, while the remaining 51.2% developed secondary effects due to a fat-soluble vitamin deficiency. An odds ratio analysis disclosed that patients diagnosed after 10 years of age have an increased risk for presenting clinical complications (OR = 18.0; 95% CI 6.0-54.1, p < 0.0001). A great diversity of mutations in MTTP has been observed (n = 76, being the most common p.G865X and p.N139_E140) and some of them with possible residual activity.
CONCLUSIONS: The first Mexican patient with abetalipoproteinemia presents a novel MTTP mutation p.Gly417Valfs*12. Three factors that could modulate the phenotype in abetalipoproteinemia were identified: age at diagnosis, treatment, and the causal mutation.
摘要：
背景：我们的目的是描述第一位患有abetalipoproteinia的墨西哥患者，并进行生化比较分析，临床,和文献报道的100例病例的遗传特征。
方法：我们对一名血脂水平极低的墨西哥女孩及其家人进行了生化和分子筛查。Further,我们整合并评估了文献中描述的abetalipoprotein血症病例的特征.
结果：我们的病人是一名6岁的女孩，她出现了呕吐，慢性腹泻,未能茁壮成长，吸收不良,棘皮细胞增多症,贫血,转氨酶升高，和极低的脂质水平。MTTP基因测序显示新突变p.Gly417Valfs*12(G缺失c.1250)的纯合性。通过对报告病例的分析,观察到60个临床特征（14个经典和46个非经典），是最常见的棘皮细胞增多症（57.5％），吸收不良（43.7%），和腹泻（42.5%）；48.8%的患者仅表现出经典的临床特征，而其余的51.2％由于脂溶性维生素缺乏而产生了副作用。比值比分析显示，10岁以后确诊的患者出现临床并发症的风险增加（OR=18.0；95%CI6.0-54.1，p<0.0001）。已经观察到MTTP中突变的巨大多样性(n=76,是最常见的p.G865X和p.N139_E140),并且它们中的一些具有可能的残留活性。
结论：首例墨西哥患者出现一种新的MTTP突变p.Gly417Valfs*12。确定了可以调节阿贝脂蛋白血症表型的三个因素：诊断时的年龄，治疗,和因果突变。
方法：我们对一名血脂水平极低的墨西哥女孩及其家人进行了生化和分子筛查。Further,我们整合并评估了文献中描述的abetalipoprotein血症病例的特征.
结果：我们的病人是一名6岁的女孩，她出现了呕吐，慢性腹泻,未能茁壮成长，吸收不良,棘皮细胞增多症,贫血,转氨酶升高，和极低的脂质水平。MTTP基因测序显示新突变p.Gly417Valfs*12(G缺失c.1250)的纯合性。通过对报告病例的分析,观察到60个临床特征（14个经典和46个非经典），是最常见的棘皮细胞增多症（57.5％），吸收不良（43.7%），和腹泻（42.5%）；48.8%的患者仅表现出经典的临床特征，而其余的51.2％由于脂溶性维生素缺乏而产生了副作用。比值比分析显示，10岁以后确诊的患者出现临床并发症的风险增加（OR=18.0；95%CI6.0-54.1，p<0.0001）。已经观察到MTTP中突变的巨大多样性(n=76,是最常见的p.G865X和p.N139_E140),并且它们中的一些具有可能的残留活性。
结论：首例墨西哥患者出现一种新的MTTP突变p.Gly417Valfs*12。确定了可以调节阿贝脂蛋白血症表型的三个因素：诊断时的年龄，治疗,和因果突变。
