Ayoub Carine, Azar Yara, Maddah Dina, Ghaleb Youmna, Elbitar Sandy, Abou-Khalil Yara, Jambart Selim, Varret Mathilde, Boileau Catherine, El Khoury Petra, Abifadel Marianne
Laboratory of Biochemistry and Molecular Therapeutics (LBTM), Faculty of Pharmacy, Pôle Technologie- Santé, Saint Joseph University of Beirut, Beirut, Lebanon.
Laboratory for Vascular Translational Science (LVTS), INSERM, Paris Cité University and Sorbonne Paris Nord University, Paris, France.
Front Genet. 2022 Aug 19;13:961028. doi: 10.3389/fgene.2022.961028. eCollection 2022.
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 and genes were sequenced and plasma PCSK9 levels were measured. Sanger sequencing of the 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 (-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 pathogenic variant and 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.
家族性乳糜微粒血症综合征是一种罕见的常染色体隐性脂蛋白代谢紊乱疾病，其特征为空腹血浆中存在乳糜微粒，且血浆甘油三酯（TG）水平显著升高，可超过22.58 mmol/L。该疾病与反复出现的腹痛和胰腺炎、疹性皮肤黄瘤病、视网膜脂血症以及肝脾肿大有关。一个移民到黎巴嫩的近亲叙利亚家庭，在发现两名儿童患有家族性乳糜微粒血症综合征后被转诊至我们实验室。对 和 基因进行了测序，并检测了血浆前蛋白转化酶枯草溶菌素9（PCSK9）水平。对 基因进行Sanger测序发现，两名患病儿童外显子5中存在纯合状态的p.(Val227Phe) 致病变体，而其他招募的家庭成员则为杂合状态。有趣的是，p.(Val227Phe) 纯合携带者的PCSK9水平比该变体杂合携带者低约50%（-值 = 0.13），且在年龄大致相同的黎巴嫩儿童样本中，PCSK9水平处于第5至第7.5百分位之间。此外，这是首次报道同时携带 致病变体和 变体（L10和L11亮氨酸插入）的个体，这两种变体分别可降低和升高低密度脂蛋白胆固醇（LDL-C）水平。两名儿童的TG水平同时波动，在从一个国家迁移到另一个国家后尤其高，而在低脂饮食下则降低。该病例对于提高公众对近亲结婚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。它还强调了这些疾病早期诊断和管理对于预防严重并发症（如家族性高乳糜微粒血症中的反复胰腺炎）的重要性。
