PDF(Pubmed)
Abstract：
Familial chylomicronemia syndrome (FCS) is a rare disorder of triglyceride (TG) metabolism caused by loss of function variants in one of five known canonical genes involved in chylomicron lipolysis and clearance-LPL, APOC2, APOA5, LMF1, and GPIHBP1. Pathogenic variants in LPL, which encodes the hydrolytic enzyme lipoprotein lipase, account for over 80%-90% of cases. FCS may present in infancy with hypertriglyceridemia-induced acute pancreatitis and is challenging to manage both acutely and in the long-term. Here, we report our experience managing two unrelated infants consecutively diagnosed with hypertriglyceridemia-induced acute pancreatitis caused by LPL deficiency. Both had elevated TGs at presentation (205 and 30 mmol/L, respectively) and molecular genetic testing confirmed each infant carried a different homozygous pathogenic variant in the LPL gene, specifically, c.987C>A (p.Tyr329Ter) and c.632C>A (p.Thr211Lys). The more severely affected infant had cutaneous xanthomata, lipemia retinalis and lipemic plasma at presentation, and required management in an intensive care setting. Acute stabilisation was achieved using insulin and heparin infusions together with the iterative implementation of a fat-restricted diet, low in long chain triglycerides (LCT) and supplemented with medium chain triglycerides (MCT). In both cases, provision of adequate caloric intake (~110-120 kcal/kg/day) was also found to be important for a sustained TG reduction during the acute phase of management. In summary, a high index of suspicion is required to diagnose FCS in infants with hypertriglyceridemia-induced acute pancreatitis, management of which can be challenging, highlighting the need for more evidence-based recommendations.
摘要：
家族性乳糜微粒血症（FCS）是一种罕见的甘油三酸酯（TG）代谢障碍，由与乳糜微粒脂解和清除LPL有关的五个已知经典基因之一的功能变体丧失引起，APOC2、APOA5、LMF1和GPIHBP1。LPL中的致病变异，它编码水解酶脂蛋白脂肪酶，占病例的80%-90%以上。FCS可能存在于高甘油三酯血症诱导的急性胰腺炎的婴儿期，并且在急性和长期管理方面都具有挑战性。这里,我们报告了我们管理两名连续诊断为由LPL缺乏引起的高甘油三酯血症诱导的急性胰腺炎的无关婴儿的经验.两者在呈递时都有升高的TG(205和30mmol/L，分别）和分子遗传测试证实每个婴儿在LPL基因中携带不同的纯合致病变异，具体来说,c.987C>A（p。Tyr329Ter）和c.632C>A（p。Thr211Lys）。受影响更严重的婴儿有皮肤黄瘤，出现时的脂血视网膜和脂血血浆，并需要在重症监护环境中进行管理。使用胰岛素和肝素输注以及反复实施脂肪限制饮食可实现急性稳定。长链甘油三酯（LCT）低，补充中链甘油三酯（MCT）。在这两种情况下，还发现提供足够的热量摄入（〜110-120kcal/kg/天）对于在治疗的急性期持续降低TG很重要。总之,高甘油三酯血症诱导的急性胰腺炎婴儿FCS的诊断需要高度怀疑。其中的管理可能是具有挑战性的，强调需要更多基于证据的建议。
