PDF(Pubmed)
Abstract：
Familial chylomicronemia syndrome is a rare autosomal recessive disorder of lipoprotein metabolism characterized by the presence of chylomicrons in fasting plasma and an important increase in plasma triglycerides (TG) levels that can exceed 22.58 mmol/l. The disease is associated with recurrent episodes of abdominal pain and pancreatitis, eruptive cutaneous xanthomatosis, lipemia retinalis, and hepatosplenomegaly. A consanguineous Syrian family who migrated to Lebanon was referred to our laboratory after perceiving familial chylomicronemia syndrome in two children. The LPL and PCSK9 genes were sequenced and plasma PCSK9 levels were measured. Sanger sequencing of the LPL gene revealed the presence of the p.(Val227Phe) pathogenic variant in exon 5 at the homozygous state in the two affected children, and at the heterozygous state in the other recruited family members. Interestingly, PCSK9 levels in homozygous carriers of the p.(Val227Phe) were ≈50% lower than those in heterozygous carriers of the variant (p-value = 0.13) and ranged between the 5th and the 7.5th percentile of PCSK9 levels in a sample of Lebanese children of approximately the same age group. Moreover, this is the first reported case of individuals carrying simultaneously an LPL pathogenic variant and PCSK9 variants, the L10 and L11 leucine insertion, which can lower and raise low-density lipoprotein cholesterol (LDL-C) levels respectively. TG levels fluctuated concomitantly between the two children, were especially high following the migration from a country to another, and were reduced under a low-fat diet. This case is crucial to raise public awareness on the risks of consanguineous marriages to decrease the emergence of inherited autosomal recessive diseases. It also highlights the importance of the early diagnosis and management of these diseases to prevent serious complications, such as recurrent pancreatitis in the case of familial hyperchylomicronemia.
摘要：
家族性乳糜微粒血症是一种罕见的脂蛋白代谢常染色体隐性遗传疾病，其特征是空腹血浆中存在乳糜微粒，血浆甘油三酯（TG）水平显着升高，可超过22.58mmol/l。该疾病与腹痛和胰腺炎的反复发作有关，发疹性皮肤黄瘤病，脂血视网膜,和肝脾肿大.在发现两个孩子的家族性乳糜微粒血症综合征后，一个移居黎巴嫩的近亲叙利亚家庭被转诊到我们的实验室。对LPL和PCSK9基因进行测序并测量血浆PCSK9水平。LPL基因的Sanger测序显示，在两个受影响的儿童中，在纯合状态下，外显子5中存在p。（Val227Phe）致病性变异体，在其他招募的家庭成员中处于杂合状态。有趣的是,p。纯合携带者的PCSK9水平。（Val227Phe）比该变体的杂合携带者（p值=0.13）低≈50％，并且在大约相同年龄段的黎巴嫩儿童样本中PCSK9水平的第5百分位数和第7.5百分位数之间。此外，这是首例同时携带LPL致病性变异体和PCSK9变异体的病例。插入L10和L11亮氨酸,可以分别降低和升高低密度脂蛋白胆固醇（LDL-C）水平。TG水平在两个孩子之间同时波动，从一个国家迁移到另一个国家后，在低脂饮食下减少。这种情况对于提高公众对近亲婚姻风险的认识，以减少遗传性常染色体隐性疾病的出现至关重要。它还强调了早期诊断和管理这些疾病以防止严重并发症的重要性，例如家族性高乳糜微粒血症的复发性胰腺炎。
