Mutations In Lipoprotein Lipase Gene Research Articles

Correlation analysis of hypertension, traditional Chinese medicine constitution, and LPL gene polymorphism in the elderly in communities in Shanghai.

Research on the genetic mechanisms of hypertension has been a hot topic in the cardiovascular field. To study the correlation between senile hypertension and traditional Chinese medicine (TCM) constitution and lipoprotein lipase (LPL) gene polymorphism and to provide the theoretical basis for TCM prevention and treatment of hypertension. The elderly population in communities in Shanghai (hypertensive: 264 cases; non-hypertensive: 159 cases) was taken as the research object. Essential data and information on TCM constitution were collected. The LPL gene mutation was detected using the second-generation sequencing method. Statistical analysis was performed to clarify the relationship between hypertension and senile hypertension. The correlation of TCM constitution with risk factors and LPL gene polymorphisms was studied. The primary TCM constitutions in the hypertension group were phlegm-dampness constitution (51.52%), yin-deficiency constitution (17.42%), balanced constitution (15.53%), and yin-deficiency (9.43%). Logistic regression analysis showed that the phlegm-dampness constitution (P< 0.05, OR = 2.587) and yin-deficiency constitution (P< 0.01, OR = 2.693) were the risk constitutions of hypertension in the elderly. A total of 37 LPL gene mutation loci (SNP: 22; new discovery: 15) were detected in the LPL gene, and the mutation rates of rs254, rs255, rs3208305, rs316, rs11570891, rs328, rs11570893, and rs13702 were relatively high, which were 26.24%, 26.24%, 16.08%, 14.66%, 13.24%, 12.06%, and 10.64%. In the phlegm-dampness group, the proportion of rs254 CC type, rs255 TT type, and rs13702 TT type in the hypertensive group (77.21%, 77.21%, and 93.38%) was higher than that in the non-hypertensive group (56.41%, 56.41%, and 82.05%), The difference was statistically significant (P< 0.05). The phlegm-dampness constitution and yin-deficiency constitution are the risk factors of hypertension in the elderly; in the phlegm-dampness population, rs254 CC type, rs255 TT type, and rs13702 TT type are the risk factors for elderly hypertension.

Clinical features and functions of a novel Lpl mutation C.986A>C (p.Y329S) in patient with hypertriglyceridemia

ObjectiveTo investigate and assess the clinical features and functions of a new lipoprotein lipase (Lpl) gene mutation c.986A>C (p.Y329S) found in hypertriglyceridemia(HTG) patients from a Chinese family. MethodsFive members of a family with the proband were diagnosed with HTG were investigated, and fasting peripheral blood was collected . The plasma was then used to measure triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein cholesterol (HDL-C), free fatty acids (FFA), and glucose tolerance. Following that, genomic deoxyribonucleic acid (DNA) was extracted from whole-blood samples using the QIAamp whole-blood DNA kit, and the coding exon regions and flanking regions of 95 dyslipidemia-related genes were captured using GenCap liquid-phase target gene capture technology. The activity of LPL and its mutation were then determined using cell assays, and the newly discovered LPL mutant was functionally analyzed. The binding site of fenofibrate and LPL, as well as the mutation, were subjected to predictive analysis. ResultsThe LPL gene's c.986A>C (p.Y329S) heterozygous mutation was discovered, and patients with the mutation had the typical phenotype of LPL deficiency and weakened LPL activity. Furthermore, this mutant has been treated with fenofibrate, and its triglyceride level is perfectly controlled and stable. The prediction analysis of the fenofibrate and LPL binding sites reveals that the wild-type system, Phe378 contributes most to the binding energy of fenofibrate. In the mutant system, Tyr394, which contributes the most to the binding energy of fenofibrate, the contribution of S329 is greater than that of Y329 (0.9∼0.7 kal/mol) . After Y329 is mutated, the hydrogen bond data of fenofibrate and LPL will also increase to quote H-bond diagrams. ConclusionsA heterozygous mutation c.986A>C (p.Y329S) in exon 6 of Lpl gene occurs in the proband with familial HTG. Lpl c.986A>C (p.Y329S) mutation weakens the activity of the LPL, which may be the pathogenic mutation of HTG. In addition, The proband has been treated with fenofibrate and the triglyceride level is ideally controlled and stable. The prediction analysis of the fenofibrate and LPL binding site shows that the wild-type system, Phe378 contributes most to the binding energy of fenofibrate. In the mutant system, Tyr394, which contributes the most to the binding energy of fenofibrate, the contribution of S329 is greater than that of Y329 (0.9∼0.7 kal/mol). After Y329 is mutated, the hydrogen bond data of fenofibrate and LPL will also increase, which may be one of the reasons why the mutation has no effect on the therapeutic effect of fenofibrate.

Volanesorsen: A New Era in the Treatment of Severe Hypertriglyceridemia.

Introduction: Familial chylomicronemia syndrome (FCS) is a rare inherited disease, mainly due to lipoprotein lipase (LPL) gene mutations, leading to lipid abnormalities. Volanesorsen, a second-generation 2′-O-methoxyethyl (2′-MOE) chimeric antisense therapeutic oligonucleotide, can decrease plasma apolipoprotein C3 and triglycerides (TG) levels through LPL-independent pathways. The European Medicines Agency has approved volanesorsen as an adjunct to diet in adult FCS patients with an inadequate response to TG-lowering therapy. Areas covered: Available clinical data on volanesorsen efficacy and safety are presented. Furthermore, we discuss the yearly treatment with volanesorsen of a 21-year-old female FCS patient with LPL mutation. Volanesorsen was well-tolerated and decreased patient’s TG levels (from >5000 mg/dL (56 mmol/L) to 350–500 mg/dL (4–5.6 mmol/L)) at 12 months. Lipoprotein apheresis (LA) was stopped and there were no episodes of pancreatitis or abdominal pain. Expert opinion: Severe hypertriglyceridemia can potentially be fatal. Until recently, there was no specific treatment for FCS, apart from hypotriglyceridemic diet, fibrates, omega-3 fatty acids, and LA sessions. Therefore, volanesorsen represents a promising therapeutic solution for these patients. The main side effect of volanesorsen therapy is thrombocytopenia, which should be monitored and treated accordingly. Increasing evidence will further elucidate the clinical implications of volanesorsen use in daily practice.

Rare novel LPL mutations are associated with neonatal onset lipoprotein lipase (LPL) deficiency in two cases

BackgroundLipoprotein lipase (LPL) deficiency is a monogenic lipid metabolism disorder biochemically characterized by hypertriglyceridemia (HTG) inherited in an autosomal recessive manner. Neonatal onset LPL deficiency is rare. The purpose of this study was to clarify the clinical features of neonatal LPL deficiency and to analyze the genetic characteristics of LPL gene.MethodsIn order to reach a definite molecular diagnose, metabolic diseases-related genes were sequenced through gene capture and next generation sequencing. Meanwhile, the clinical characteristics and follow-up results of the two newborns were collected and analyzed.ResultsThree different mutations in the LPL gene were identified in the two newborns including a novel compound heterozygous mutation (c.347G > C and c.472 T > G) and a reported homozygous mutation (c.836 T > G) was identified. Interestingly, both the two neonatal onset LPL deficiency patients presented with suffered recurrent infection in the hyperlipidemia stage, which was not usually found in childhood or adulthood onset LPL deficiency patients.ConclusionThe two novel mutaitons, c.347G > C and c.472 T > G, identified in this study were novel, which expanded the LPL gene mutation spectrum. In addition, suffered recurrent infection in the hyperlipidemia stage implied a certain correlation between immune deficiency and lipid metabolism abnormality. This observation further supplemented and expanded the clinical manifestations of LPL deficiency.

A non-integrated iPSC line (SDQLCHi042-A) from a boy suffering from familial combined hyperlipidemia with compound heterozygous mutations of lipoprotein lipase gene

In this study, peripheral blood monouclear cells (PBMCs) were donated from a boy suffering from familial combined hyperlipidemia confirmed by clinical and genetic diagnosis, which carried compound heterozygous mutations of lipoprotein lipase (LPL) gene. The induced pluripotent stem cell (iPSC) was generated with non-integrated episomal vectors carrying OCT4, SOX2, KLF4, BCL-XL and C-MYC. The iPSCs presented the morphology of pluripotent cells, highly expressed mRNA and protein of pluripotent markers, excellent differentiation potency in vitro and normal karyotype, and bore LPL gene mutations.

Analysis of a Chinese Pedigree With Familial Chylomicronemia Syndrome Reveals Two Novel LPL Mutations by Whole-Exome Sequencing

Familial chylomicronemia syndrome (FCS) is a rare monogenic autosomal recessive disease caused by loss-of-function mutations in genes involved in chylomicron breakdown through hydrolysis of triglycerides into free fatty acids. Patients are often diagnosed in early childhood with extremely high triglyceride levels and symptoms including abdominal pain, eruptive cutaneous xanthomata, hepatosplenomegaly, and significant cognitive, psychological, and social impairment. The most serious medical condition suffered by FCS patients is recurrent acute pancreatitis. Lipoprotein lipase (LPL) gene mutation accounts for majority of the known pathogenic mutations. Early diagnosis and strict low-fat diet are critical for successful management of the triglyceride concentration to lower the risk of pancreatitis. The true prevalence of FCS in China is unknown and here we report a Chinese female preterm neonate presented with an extremely high triglyceride level of 22.11 mmol/L on day 13 after birth. Clinical and laboratory workup including whole-exome sequencing revealed two novel compound heterozygous LPL mutations (c.406G > C and c.829G > C) that are co-segregated with her non-consanguineous parents, consistent with autosomal recessive inheritance. A diagnosis of FCS based on clinical, biochemical, and genetic ground was made to guide her management.

Lpl-C310R mutation is associated with impaired glucose tolerance and endoplasmic reticulum stress in skeletal muscle

Primary Hypertriglyceridemia refers to a loss-of-function genetic defect which prevents the triglyceride (TG) in chylomicrons (CM) from lipolysis, leading to the accumulation of TG. The mutation of lipoprotein lipase (LPL) gene has been recognized as the main cause of primary hypertriglyceridemia. Recently, a new LPL gene mutation p.C310R(c. T928C) was identified in a family with hypertriglyceridemia. The proband was manifested by severe hypertriglyceridemia and diabetes. Skeletal muscle is the major LPL-synthesizing tissue and insulin response target tissue. However, little is known about the effects of LPL gene mutation on skeletal muscle. This study is intended to observe the effects of LPL-C310R mutation on glycolipid metabolism and skeletal muscle. We found that a significantly decreased LPL plasma concentration, activity and the expression levels in skeletal muscle were observed in LplC310R/+ mice comparing to wild type mice. Those mutant mice also exhibited increased fasting plasma TG, free fat acids (FFA) and insulin, as well as FFA in muscle, and decreased glucose tolerance. Enhanced expression of BIP and elevated phosphorylation of IRE1α were observed in skeletal muscle, suggesting increased endoplasmic reticulum stress (ERS). Consistent with this, increased phosphorylation of JNK was also observed. Meanwhile, remarkably enhanced phosphorylation of IRS-1 (Ser307) and decreased phosphorylation of AKT were observed in skeletal muscle of mutant mice, suggesting impaired insulin signaling. Significant lipid deposition and morphological changes in endoplasmic reticulum and mitochondria were observed in the skeletal muscle of mutant mice but not in wild type control. Results demonstrate Lpl C310R mutation caused impaired glucose tolerance, ER stress and impaired insulin signaling in skeletal muscle.

Dyslipidemia: Genetics, lipoprotein lipase and HindIII polymorphism.

The direct link between lipid metabolism alterations and the increase of cardiovascular risk are well documented. Dyslipidemias, including isolated high LDL-c or mixed dyslipidemia, such as those seen in diabetes (hypertriglyceridemia, high LDL-c or low HDL-c), correlate with a significant risk of cardiovascular and cerebrovascular disease worldwide. This review analyzes the current knowledge concerning the genetic basis of lipid metabolism alterations, emphasizing lipoprotein lipase gene mutations and the HindIII polymorphism, which are associated with decreased levels of triglycerides and LDL-c, as well as higher levels of HDL-c. These patterns would be associated with decreased global morbidity and mortality, providing protection against cardiovascular and cerebrovascular diseases.

Neonatal hyperlipidemia with pancreatitis

Lipoprotein lipase (LPL) deficiency is an autosomal recessive metabolic disorder with varying presentation in infancy and childhood, whereas clinical manifestations are rare in neonatal period. The estimated prevalence is one in a million births. A 23-day-old baby was admitted with complaints of fever, vomiting, and lethargy. Blood sample drawn appeared lipemic. Lipemia retinalis was noted on funduscopic examination. Biochemical analysis revealed abnormal lipid profile with severe hypertriglyceridemia (10,300 mg/dL) and elevated serum lipase level (517 IU/L) indicative of LPL deficiency with acute pancreatitis. LPL deficiency was suspected and was confirmed by molecular genetic testing, which revealed a novel mutation in LPL gene. Dietary management and gemfibrozil were started following which serum triglyceride level decreased and serum lipase level normalized. The patient is following up regularly for growth and development monitoring.

Dyslipidemia: Genetics, lipoprotein lipase and HindIII polymorphism.

The direct link between lipid metabolism alterations and the increase of cardiovascular risk are well documented. Dyslipidemias, including isolated high LDL-c or mixed dyslipidemia, such as those seen in diabetes (hypertriglyceridemia, high LDL-c or low HDL-c), correlate with a significant risk of cardiovascular and cerebrovascular disease worldwide. This review analyzes the current knowledge concerning the genetic basis of lipid metabolism alterations, emphasizing lipoprotein lipase gene mutations and the HindIII polymorphism, which are associated with decreased levels of triglycerides and LDL-c, as well as higher levels of HDL-c. These patterns would be associated with decreased global morbidity and mortality, providing protection against cardiovascular and cerebrovascular diseases.

Molecular and functional characterization of familial chylomicronemia syndrome

Background and aimsFamilial chylomicronemia syndrome is a rare autosomal recessive disorder leading to severe hypertriglyceridemia (HTG) due to mutations in lipoprotein lipase (LPL)-associated genes. Few data exist on the clinical features of the disorder or on comprehensive genetic approaches to uncover the causative genes and mutations. MethodsEight patients diagnosed with familial hyperchylomicronemia with recessive inheritance were included in this study (two males and six females; median age of onset 23.0 years; mean triglyceride level 3446 mg/dl). We evaluated their clinical features, including coronary artery disease using coronary computed tomography, and performed targeted next-generation sequencing on a panel comprising 4813 genes associated with known clinical phenotypes. After standard filtering for allele frequency <1% and in silico annotation prediction, we used three types of variant filtering to identify causative mutations: homozygous mutations in known familial hyperchylomicronemia-associated genes, homozygous mutations with high damaging scores in novel genes, and deleterious mutations within 37 genes known to be associated with HTG. ResultsA total of 1810 variants out of the 73,389 identified with 94.3% mean coverage (×20) were rare and nonsynonymous. Among these, our schema detected four pathogenic or likely pathogenic mutations in the LPL gene (p.Ala248LeufsTer4, p.Arg270Cys, p.Ala361Thr, and p.Val227Gly), including one novel mutation and a variant of uncertain significance. Patients harboring LPL gene mutations showed no severe atherosclerotic changes in the coronary arteries, but recurrent pancreatitis with long-term exposure to HTG was observed. ConclusionsThese results demonstrate that LPL gene plays a major role in extreme HTG associated with hyperchylomicronemia, although the condition may not cause severe atherosclerosis.

Lipoprotein Lipase (LPL) Gene Mutation: A First Report in Children

Genetic hyperchylomicronemia is a rare autosomal recessive disorder of lipoprotein metabolism estimated to affect approximately one per million individuals. We report a case with a rare mutation identified. It’s a genetic chylomicronemia in a Moroccan newborn baby, with massive hypertriglyceridemia and clinical signs of acute pancreatitis. She was a newborn female, first-degree of consanguineous parents. She was hospitalized for hypertriglyceridemia, complicated by acute pancreatitis; serum was noted to be milky. The genetic study found a mutation of the Lipoprotein Lipase (LPL) gene: homozygous pathogenic variant c.1019-3C > A. She enjoyed good health, developed well and the triglyceride was maintained at a concentration of

Abstract 11169: Whole Exome Sequencing in Subjects With Mendelian Form of Primary Severe Hypertriglyceridemia

Background: Few data exist regarding clinical application of whole exome sequencing (WES) for the molecular diagnosis of the subjects with Mendelian form of primary severe hypertriglyceridemia (HTG). Methods: WES was performed on 28 individuals exhibiting severe HTG (≥ 1,000 mg/dl) without any transient causes (15 men, mean age 42 ± 20 yr, median triglyceride 1,756 mg/dl [interquartile range 1,288-2,443]) followed by recessive and dominant inheritance modeling in known monogenic HTG genes and disease-network candidate analysis gene ranking to identify a causative mutation(s), including novel underlying genetic mechanism for severe HTG. Results: Using our schema, we identified possible causative mutation(s) in 14 individuals (50%). Among them, we identified 2 individuals with lipoprotein lipase (LPL) deficiency with double mutations in LPL gene, and 2 individuals with a heterozygous mutation carrier in LPL gene. Moreover, we identified one individual harboring a double mutations in LPL gene and APOA5 gene. Also we identified one individual with a heterozygous mutation in lipase maturation factor 1 (LMF1) gene, which is rarer form of familial hyperchylomicronemia, and 2 individuals with type 3 hyperlipidemia harboring mutations in APOE gene, including novel ones. Interestingly, we also identified 6 other individuals harboring a deleterious mutation in cyclic AMP-responsive element-binding protein 3-like protein 3 (CREB3L3), MLX Interacting Protein-Like (MLXIPL), SLC25A40 genes, glucokinase regulatory protein (GCKR), possibly associated with this extreme phenotype. Conclusion: We identified potential causative mutations in 14 among 28 individuals (50%) with severe HTG within the coding region of the genes known to cause rare Mendelian dyslipidemias. Clinical WES is now feasible where molecular diagnoses could be made in such extreme cases, which could potentially provide appropriate therapies.

Type Ⅰ hyperlipoproteinemia caused by lipoprotein lipase gene mutation in three Chinese children

Type Ⅰ hyperlipoproteinemia caused by lipoprotein lipase gene mutation in three Chinese children

Novel mutations in the GPIHBP1 gene identified in 2 patients with recurrent acute pancreatitis

Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) has been demonstrated to be essential for the invivo function of lipoprotein lipase (LPL), the major triglyceride (TG)-hydrolyzing enzyme involved in the intravascular lipolysis of TG-rich lipoproteins. Recently, loss-of-function mutations of GPIHBP1 have been reported as the cause of type I hyperlipoproteinemia in several patients. Two unrelated patients were referred to our Lipid Units because of a severe hypertriglyceridemia and recurrent pancreatitis. We measured LPL activity in postheparin plasma and serum ApoCII and sequenced LPL, APOC2, and GPIHBP1. The 2 patients exhibited very low LPL activity not associated with mutations in LPL gene or with ApoCII deficiency. The sequence of GPIHBP1 revealed 2 novel point mutations. One patient (proband 1) was found to be homozygous for a C>A transversion in exon 3 resulting in the conversion of threonine to lysine at position 80 (p.Thr80Lys). The other patient (proband 2) was found to be homozygous for a G>T transversion in the third base of the ATG translation initiation codon in exon 1, resulting in the conversion of methionine to isoleucine (p.Met1Ile). In conclusion, we have identified 2 novel GPIHBP1 missense mutations in 2 unrelated patients as the cause of their severe hypertriglyceridemia.

High-resolution melting curve analysis of the ADSL and LPL genes and their correlation with meat quality and blood parameters in chickens.

Adenylosuccinate lyase (ADSL) and lipoprotein lipase (LPL) are key enzymes in the metabolism of inosine monophosphate (IMP) and fat mass, which are important factors in meat quality evaluation. In this study, we selected 50 hens from the ISA B-line layers and Guangxi Yellow chickens, slaughtered the chickens at 120 days old, and analyzed polymorphisms in the ADSL and LPL genes using the high-resolution melting curve method. Blood lipid parameters, intramuscular fat (IMF), and IMP content were higher (P < 0.05) in Guangxi Yellow chickens than in ISA B-line layers, while LPL activity was lower (P < 0.05). In exon 2 of the ADSL gene, a C3484T mutation was identified. In both breeds, the CC genotype showed the highest IMP, and IMP was the lowest in the TT genotype. In the 5ꞌ regulatory region of the LPL gene, a C293T mutation was identified. In both breeds, the CC genotype showed the lowest LPL and IMF, while IMF was the highest in the TT genotype. The percentages of individuals with the TT type in the ADSL gene, which was associated with the lowest IMP, were 16.0 and 52.0% in Guangxi chickens and ISA layers, respectively. The percentages of individuals with the CC type of the LPL gene, which was associated with the lowest LPL and IMF, were 28.0 and 44.0%, respectively. The ADSL and LPL gene mutations are correlated with differences in meat quality in different chicken breeds, and high-resolution melting curve is an effective prediction technology for these mutations.

Compound heterozygous deletions presenting as infantile chylomicronemia

Introduction: Monogenic disorders affecting the lipid metabolism are rare, but early diagnosis is important to ensure prompt initiation of management. case report: A three-week old neonate presenting with rectal bleeding was found to have blood of an unusual cream-like appearance. significant lipemia was confirmed, with massive increase in triglyceride and cholesterol levels. centrifugation confirmed chylomicronemia. Primary chylomicronemia is extremely rare and most commonly caused by a lipoprotein lipase (LPL) gene mutation. the infant was a compound heterozygous for two deletions in the LPL gene: p. thr45HisfsX3, and the here for the first time described p. Phe189X, both leading to a premature stop codon the absence of a mature protein. subsequent change to medium chain triglyceride feed resulted in near-normal blood lipid levels. conclusion: Novel mutations affecting chylomicron metabolism continue to be identified and may affect patients of ethnic background considered low-risk. this case illustrates that adequate treatment and dietary management is highly effective in 1 , Geesje Dallinga-Thie 2 , Shankar

A 3-day-old neonate with severe hypertriglyceridemia from novel mutations of the GPIHBP1 gene.

Familial chylomicronemia is a genetic defect of the intravascular lipolysis of triglyceride (TG)-rich lipoproteins. Intravascular lipolysis involves the TG-hydrolase lipoprotein lipase (LPL) as well as other factors such as apolipoprotein CII and apolipoprotein AV (activators of LPL), GPIHBP1 (the molecular platform required for LPL activity on endothelial surface), and LMF1 (a factor required for intracellular formation of active LPL). We sequenced the familial chylomicronemia candidate genes in a neonate with chylomicronemia. A 3-day-old newborn was found to have chylomicronemia (plasma TG 18.8mmol/L, 1.667mg/dL). The discontinuation of breastfeeding for 24hours reduced plasma TG to 2.3mmol/L (201mg/dL), whereas its resumption induced a sharp TG increase (7.9mmol/L, 690mg/dL). The child was switched to a low-fat diet, which was effective in maintaining TG level below 3.5mmol/L (294mg/dL) during the first months of life. The child was found to be a compound heterozygous for 2 novel mutations in GPIHBP1 gene. The first mutation was a 9-bp deletion and 4-bp insertion in exon 2, causing a frameshift that abolished the canonical termination codon TGA. The predicted translation product of the mutant messenger RNA is a peptide that contains 51 amino acids of the N-terminal end of the wild-type protein followed by 252 novel amino acids. The second mutation was a nucleotide change (c.319T>C), causing an amino acid substitution p.(Ser107Pro) predicted in silico to be damaging. GPIHBP1 mutations should be considered in neonates with chylomicronemia negative for mutations in LPL gene.

A novel lipoprotein lipase gene missense mutation in Chinese patients with severe hypertriglyceridemia and pancreatitis

BackgroundAlterations or mutations in the lipoprotein lipase (LPL) gene contribute to severe hypertriglyceridemia (HTG). This study reported on two patients in a Chinese family with LPL gene mutations and severe HTG and acute pancreatitis.MethodsTwo patients with other five family members were included in this study for DNA-sequences of hyperlipidemia-related genes (such as LPL, APOC2, APOA5, LMF1, and GPIHBP1) and 43 healthy individuals and 70 HTG subjects were included for the screening of LPL gene mutations.ResultsBoth patients were found to have a compound heterozygote for a novel LPL gene mutation (L279V) and a known mutation (A98T). Furthermore, one HTG subject out of 70 was found to carry this novel LPL L279V mutation.ConclusionsThe data from this study showed that compound heterozygote mutations of A98T and L279V inactivate lipoprotein lipase enzymatic activity and contribute to severe HTG and acute pancreatitis in two Chinese patients. Further study will investigate how these LPL gene mutations genetically inactivate the LPL enzyme.

Lipoprotein-Lipase Deficiency: Treatment with Omega-3 Fatty Acids and Colestyramine for Severe Gestational Hypertriglyceridaemia and Follow up over Twenty Years

We describe the case of a Chinese woman with lipoprotein lipase (LPL) deficiency treated with omega-3 fatty acids and colestyramine during pregnancy at the age of 31 years, and her subsequent management with other lipid regulating drugs over the following 21 years. The coexistence of LPL gene and ApoA2 gene mutations, gestational diabetes and ApoE 2 heterozygosity resulted in marked hypertriglyceridemia and acute pancreatitis during her fourth pregnancy. Treatment of the severe gestational hypertriglyceridaemia with omega-3 fatty acids was effective during pregnancy before the introduction of colestyramine. Our findings indicate that colestyramine should not be used in pregnancy as it may increase triglyceride levels and cause acute pancreatitis. After this pregnancy she was managed using a combination of lipid regulating drugs. Gene replacement therapy for LPL deficiency provides hope as a future effective therapy for this rare serious inherited condition.