PDF(Pubmed)
Abstract：
UNASSIGNED: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder, typically caused by biallelic pathogenic variants in the lipoprotein lipase (LPL) gene. Lipoprotein lipase, encoded by the LPL gene, catalyzes the hydrolysis of triglycerides, and its deficiency or dysfunction can lead to chylomicronemia and potentially fatal recurrent acute pancreatitis.
UNASSIGNED: Here, we report an Asian child with FCS due to compound heterozygous LPL variants. The 4-year-old patient presented with splenomegaly and severe hypertriglyceridemia, specifically chylomicronemia which resulted in abnormal coagulation measured by a turbidity-based assay. Based on the clinical features and family history, the diagnosis of FCS was suspected, and confirmed by the identification of compound heterozygous variants in the LPL gene (c.461A>G; p.His154Arg and c.788T>A; p.Leu263Gln) in the patient, inheriting one from each parent. According to the clinical and genetic findings, the patient was diagnosed with FCS. In vitro experimental validation found that the LPL p.H154R variant reduced the expression of lipoprotein lipase and decreased its lipolytic activity, while the LPL p.L263Q variant mainly impaired its lipolytic activity.
UNASSIGNED: FCS was molecularly diagnosed using whole exome sequencing in the case presented. When interpreting abnormal coagulation profiles measured by turbidity-based assay, the possibility of lipemic blood (or chylomicronemia) should be considered and the presence of this phenomenon might indicate the diagnosis of FCS. In vitro experiments showed that the two LPL variants impaired lipoprotein lipase expression and/or function making them likely to be pathogenic.
UNASSIGNED: Here, we report an Asian child with FCS due to compound heterozygous LPL variants. The 4-year-old patient presented with splenomegaly and severe hypertriglyceridemia, specifically chylomicronemia which resulted in abnormal coagulation measured by a turbidity-based assay. Based on the clinical features and family history, the diagnosis of FCS was suspected, and confirmed by the identification of compound heterozygous variants in the LPL gene (c.461A>G; p.His154Arg and c.788T>A; p.Leu263Gln) in the patient, inheriting one from each parent. According to the clinical and genetic findings, the patient was diagnosed with FCS. In vitro experimental validation found that the LPL p.H154R variant reduced the expression of lipoprotein lipase and decreased its lipolytic activity, while the LPL p.L263Q variant mainly impaired its lipolytic activity.
UNASSIGNED: FCS was molecularly diagnosed using whole exome sequencing in the case presented. When interpreting abnormal coagulation profiles measured by turbidity-based assay, the possibility of lipemic blood (or chylomicronemia) should be considered and the presence of this phenomenon might indicate the diagnosis of FCS. In vitro experiments showed that the two LPL variants impaired lipoprotein lipase expression and/or function making them likely to be pathogenic.
摘要：
未经证实：家族性乳糜微粒血症（FCS）是一种罕见的常染色体隐性遗传疾病，通常由脂蛋白脂肪酶（LPL）基因的双等位基因致病变体引起。脂蛋白脂肪酶,由LPL基因编码，催化甘油三酯的水解，其缺乏或功能障碍可导致乳糜微粒血症和潜在致命的复发性急性胰腺炎。
未经评估：这里，我们报告了一名亚洲儿童因复合杂合子LPL变异而出现FCS。4岁患者出现脾肿大和严重的高甘油三酯血症，特别是乳糜微粒血症，通过基于浊度的测定法测量导致异常凝血。根据临床特征和家族史，怀疑FCS的诊断，并通过鉴定患者的LPL基因中的复合杂合变体（c.461A>G;p.His154Arg和c.788T>A;p.Leu263Gln）来证实，从每个父母那里继承一个。根据临床和遗传发现，患者被诊断为FCS。体外实验验证发现，LPLp.H154R变体降低了脂蛋白脂肪酶的表达，降低了其脂解活性，而LPLp.L263Q变体主要损害其脂肪分解活性。
UNASSIGNED：在所介绍的病例中，使用全外显子组测序对FCS进行分子诊断。在解释通过基于浊度的测定法测量的异常凝血曲线时，应考虑血脂血症（或乳糜微粒血症）的可能性，这种现象的存在可能表明FCS的诊断。体外实验表明，这两种LPL变体损害了脂蛋白脂肪酶的表达和/或功能，使它们可能具有致病性。
未经评估：这里，我们报告了一名亚洲儿童因复合杂合子LPL变异而出现FCS。4岁患者出现脾肿大和严重的高甘油三酯血症，特别是乳糜微粒血症，通过基于浊度的测定法测量导致异常凝血。根据临床特征和家族史，怀疑FCS的诊断，并通过鉴定患者的LPL基因中的复合杂合变体（c.461A>G;p.His154Arg和c.788T>A;p.Leu263Gln）来证实，从每个父母那里继承一个。根据临床和遗传发现，患者被诊断为FCS。体外实验验证发现，LPLp.H154R变体降低了脂蛋白脂肪酶的表达，降低了其脂解活性，而LPLp.L263Q变体主要损害其脂肪分解活性。
UNASSIGNED：在所介绍的病例中，使用全外显子组测序对FCS进行分子诊断。在解释通过基于浊度的测定法测量的异常凝血曲线时，应考虑血脂血症（或乳糜微粒血症）的可能性，这种现象的存在可能表明FCS的诊断。体外实验表明，这两种LPL变体损害了脂蛋白脂肪酶的表达和/或功能，使它们可能具有致病性。
