Familial chylomicronemia syndrome: case reports of siblings with deletions of the GPIHBP1 gene.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare monogenic form of severe hypertriglyceridemia, caused by mutations in genes involved in triglyceride metabolism. Herein, we report the case of a Korean family with familial chylomicronemia syndrome caused by compound heterozygous deletions of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). CASE PRESENTATION: A 4-year-old boy was referred for the evaluation of severe hypertriglyceridemia (3734 mg/dL) that was incidentally detected 4 months prior. His elder brother also demonstrated an elevated triglyceride level of 2133 mg/dL at the age of 9. Lipoprotein electrophoresis revealed the presence of chylomicrons, an increase in the proportion of pre-beta lipoproteins, and low serum lipoprotein lipase levels. The patient's parents and first elder brother had stable lipid profiles. For suspected FCS, genetic testing was performed using the next-generation sequencing-based analysis of 31 lipid metabolism-associated genes, which revealed no pathogenic variants. However, copy number variant screening using sequencing depth information suggested large heterozygous deletion encompassing all the coding exons of GPIHBP1. A real-time quantitative polymerase chain reaction was performed to validate the deletion site. The results showed that the siblings had two heterozygous copy number variants consisting of the whole gene and an exon 4 deletion, each inherited from their parents. During the follow-up period of 17 months, the patient did not develop pancreatitis, following dietary intervention. CONCLUSION: These siblings' case of familial chylomicronemia syndrome caused by rare GPIHBP1 deletions highlight the implementation of copy number variants-beyond next-generation sequencing-as an important consideration in diagnosis. Accurate genetic diagnosis is necessary to establish the etiology of severe hypertriglyceridemia, which increases the risk of pancreatitis.

Qualitative development of the PROMIS Profile v1.0-Familial Chylomicronemia Syndrome (FCS) 28.

PURPOSE: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by high triglyceride levels, significant disease burden, and negative impacts on health-related quality of life. This project aimed to create a PROMIS-based patient-reported outcome measure that represents valid and important concerns for patients with FCS. METHODS: We reviewed the literature and data from a previous qualitative study of FCS to identify key FCS symptoms and impacts, which were mapped to PROMIS domains to create a pool of eligible items. Candidate items were reduced per expert feedback and patients with FCS completed cognitive interviews to confirm content validity and measure content. RESULTS: Literature and qualitative data review identified ten key symptoms and 12 key impacts of FCS, including abdominal pain, fatigue, difficulty thinking, and worry about pancreatitis attacks. We identified 96 items primarily from PROMIS, supplemented with items from the Quality of Life in Neurological Disorders™ (Neuro-QoL™) and the Functional Assessment of Chronic Illness Therapy (FACIT) measurement systems. This pool was reduced to 32 candidate items, which were assessed via cognitive interviews with eight participants with FCS. Cognitive interview results and additional expert feedback led to the removal of four items and finalization of the PROMIS Profile v1.0-familial chylomicronemia syndrome (FCS) 28. CONCLUSIONS: The PROMIS Profile v1.0-familial chylomicronemia syndrome (FCS) 28 provides strong content validity for assessing quality of life among patients with FCS. The benefits of PROMIS, including norm-referenced mean values for each measure, will facilitate comparison of patients with FCS to other clinical populations.

Analyses of familial chylomicronemia syndrome in Pereira, Colombia 2010-2020: a cross-sectional study.

BACKGROUND AND AIM: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder caused by mutations in genes involved in chylomicron metabolism. On the other hand, multifactorial chylomicronemia syndrome (MCS) is a polygenic disorder and the most frequent cause of chylomicronemia, which results from the presence of multiple genetic variants related to chylomicron metabolism, in addition to secondary factors. Indeed, the genetic determinants that predispose to MCS are the presence of a heterozygous rare variant or an accumulation of several SNPs (oligo/polygenic). However, their clinical, paraclinical, and molecular features are not well established in our country. The objective of this study was to describe the development and results of a screening program for severe hypertriglyceridemia in Colombia. METHODS: A cross-sectional study was performed. All patients aged >18 years with triglyceride levels ≥500 mg/dL from 2010 to 2020 were included. The program was developed in three stages: 1. Review of electronic records and identification of suspected cases based on laboratory findings (triglyceride levels ≥500 mg/dL); 2. Identification of suspected cases based on laboratory findings that also allowed us to exclude secondary factors; 3. Patients with FCS scores <8 were excluded. The remaining patients underwent molecular analysis. RESULTS: In total, we categorized 2415 patients as suspected clinical cases with a mean age of 53 years, of which 68% corresponded to male patients. The mean triglyceride levels were 705.37 mg/dL (standard deviation [SD] 335.9 mg/dL). After applying the FCS score, 2.4% (n = 18) of patients met the probable case definition and underwent a molecular test. Additionally, 7 patients had unique variants in the APOA5 gene (c.694 T > C; p. Ser232Pro) or in the GPIHBP1 gene (c.523G > C; p. Gly175Arg), for an apparent prevalence of familial chylomicronemia in the consulting population of 0.41 per 1.000 patients with severe HTG measurement. No previously reported pathogenic variants were detected. CONCLUSION: This study describes a screening program for the detection of severe hypertriglyceridemia. Although we identified seven patients as carriers of a variant in the APOA5 gene, we diagnosed only one patient with FCS. We believe that more programs of these characteristics should be developed in our region, given the importance of early detection of this metabolic disorder.

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This report presents a case of a male infant, aged 32 days, who was admitted to the hospital due to 2 days of bloody stools and 1 day of fever. Upon admission, venous blood samples were collected, which appeared pink. Blood biochemistry tests revealed elevated levels of triglycerides and total cholesterol. The familial whole genome sequencing revealed a compound heterozygous variation in the LPL gene, with one variation inherited from the father and the other from the mother. The patient was diagnosed with lipoprotein lipase deficiency-related hyperlipoproteinemia. Acute symptoms including bloody stools, fever, and bloody ascites led to the consideration of acute pancreatitis, and the treatment involved fasting, plasma exchange, and whole blood exchange. Following the definitive diagnosis based on the genetic results, the patient was given a low-fat diet and received treatment with fat-soluble vitamins and trace elements, as well as adjustments to the feeding plan. After a 4-week hospitalization, the patient's condition improved and he was discharged. Follow-up showed a decrease in triglycerides and total cholesterol levels. At the age of 1 year, the patient's growth and psychomotor development were normal. This article emphasizes the multidisciplinary diagnosis and treatment of familial hyperlipoproteinemia presenting with symptoms suggestive of acute pancreatitis, including bloody ascites, in the neonatal period.

Causes, clinical findings and therapeutic options in chylomicronemia syndrome, a special form of hypertriglyceridemia.

The prevalence of hypertriglyceridemia has been increasing worldwide. Attention is drawn to the fact that the frequency of a special hypertriglyceridemia entity, named chylomicronemia syndrome, is variable among its different forms. The monogenic form, termed familial chylomicronemia syndrome, is rare, occuring in 1 in every 1 million persons. On the other hand, the prevalence of the polygenic form of chylomicronemia syndrome is around 1:600. On the basis of the genetical alterations, other factors, such as obesity, alcohol consumption, uncontrolled diabetes mellitus and certain drugs may significantly contribute to the development of the multifactorial form. In this review, we aimed to highlight the recent findings about the clinical and laboratory features, differential diagnosis, as well as the epidemiology of the monogenic and polygenic forms of chylomicronemias. Regarding the therapy, differentiation between the two types of the chylomicronemia syndrome is essential, as well. Thus, proper treatment options of chylomicronemia and hypertriglyceridemia will be also summarized, emphasizing the newest therapeutic approaches, as novel agents may offer solution for the effective treatment of these conditions.

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

BACKGROUND: Lipoprotein 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. METHODS: In 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. RESULTS: Three 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. CONCLUSION: The 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.

Familial chylomicronemia syndrome: an under-recognized cause of severe hypertriglyceridaemia.

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder of chylomicron metabolism causing severe elevation of triglyceride (TG) levels (>10 mmol L-1 ). This condition is associated with a significant risk of recurrent acute pancreatitis (AP). AP caused by hypertriglyceridaemia (HTG) has been associated with a worse prognosis and higher mortality rates compared to pancreatitis of other aetiology. Despite its association with poor quality of life and increased lifelong risk of HTG-AP, few healthcare providers are familiar with FCS. Because this condition is under-recognized, the majority of FCS patients are diagnosed after age 20 often after consulting several physicians. Although other forms of severe HTG such as multifactorial chylomicronemia have been associated with high atherosclerotic cardiovascular disease (ASCVD) risk and metabolic abnormalities, ASCVD and metabolic syndrome are not usually observed in FCS patients. Because FCS is a genetic condition, the optimal diagnosis strategy remains genetic testing. The presence of bi-allelic pathogenic mutations in LPL, APOC2, GPIHBP1, APOA5 or LMF1 genes confirms the diagnosis. However, some cases of FCS caused by autoantibodies against LPL or GPIHBP1 proteins have also been reported. Furthermore, a clinical score for the diagnosis of FCS has been proposed but needs further validation. Available treatment options to lower triglycerides such as fibrates or omega-3 fatty acids are not efficacious in FCS patients. Currently, the cornerstone of treatment remains a lifelong very low-fat diet, which prevents the formation of chylomicrons. Finally, inhibitors of apo C-III and ANGPTL3 are in development and may eventually constitute additional treatment options for FCS patients.

Evaluation of the chylomicron-TG to VLDL-TG ratio for type I hyperlipoproteinemia diagnostic.

BACKGROUND: The aim of this study is to confirm the diagnostic performance of the Chylomicron to very low-density lipoproteins triglycerides (CM/VLDL-TG) ratio, the triglycerides to cholesterol ratio (TG/TC) and a dichotomic rule including the tryglycerides to apolipoprotein B (TG/APOB) ratio for the presence of Type I hyperlipoproteinemia (HPLI) in patients with severe hypertriglyceridemia (sHTG) that were at high risk for familial chylomicronemia syndrome (FCS). METHODS: Two cohorts (derivation and validation) of patients with sHTG were included in the study. Anthropometric, clinical, biochemical and genetic data were obtained. The CM/VLDL-TG, TG/TC and TG/APOB ratios were calculated. Finally, a diagnostic performance study was developed to establish sensitivity, specificity and cut-offs by a ROC curve analysis in the derivation cohort as well as agreement and predictive values in the validation cohort. RESULTS: Patients with FCS in both cohorts showed an earlier presence in pancreatitis, greater number of acute pancreatitis episodes and lower BMI. FCS patients also showed higher ratios of CM/VLDL-TG, TG/TC and TG/APOB ratios, whereas their HDL-C, LDL-C and APOB levels were lower than in non-FCS patients. Sensitivity and agreement were low for both the TG/TC and TG/APOB ratios, although predictive values were good. The CM/VLDL-TG ratio showed greatest sensitivity, specificity, agreement and predictive values for cut-off of 3.8 and 4.5. CONCLUSIONS: Our results suggest that in subjects at high risk of FCS a total serum TG/TC ratio or TG/APOB ratio are feasible to initially screen for HLPI; however, a CM/VLDL-TG ratio ≥4.5 is a better diagnostic criterion for HPLI.

Familial Chylomicronemia Syndrome (FCS): Recent Data on Diagnosis and Treatment.

PURPOSE OF REVIEW: Familial chylomicronemia syndrome (FCS) is a rare recessive genetic disorder often underdiagnosed with potentially severe clinical consequences. In this review, we describe the clinical and biological characteristics of the disease together with its main complication, i.e., acute pancreatitis. We focused the paper on new diagnostic tools, progress in understanding the role of two key proteins (apolipoprotein CIII (apo CIII) and angiopoietin-like3 (ANGPTL-3)), and new therapeutic options. RECENT FINDINGS: Recently, a new diagnostic tool has been proposed by European experts to help identify these patients. This tool with two recently identified parameters (low LDL and low body mass index) can help identify patients who should be genetically tested or who may have the disease when genetic testing is not available. FCS is caused by homozygous or compound heterozygous mutations of lipoprotein lipase, apolipoprotein C-II, apolipoprotein A-V, glycosylphosphatidylinositol anchored high-density lipoprotein-binding protein 1, and lipase maturation factor. Two proteins have been identified as important player in the metabolism of triglyceride-rich lipoprotein and its regulation. These two proteins are therapeutic target. Antisense oligonucleotide targeting apo CIII has been shown to significantly decrease triglyceride levels even in FCS and is the first available treatment for these patients. Further development might identify new compounds with reduced risk to develop severe thrombocytopenia. ANGPTL-3 inhibitors have not yet been tested in FCS patients but exert significant hypotriglyceridemic effect in the more frequent and less severe polygenic forms. Beyond these two new targets, microsomal triglyceride transfer protein (MTTP) inhibitors could also be part of the armamentarium, if on-going trials confirm their efficacy. New clinical tools and simple criteria can help select patients with possible FCS and identify patients who should have a genetic testing. Identifying patients with FCS is a major issue since these patients have a high risk to suffer severe episodes of acute pancreatitis and may now benefit from new therapeutic options including antisense oligonucleotide targeting apo CIII.

Management of a pregnant patient with chylomicronemia from a novel mutation in GPIHBP1: a case report.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive lipid disorder often associated with recurrent episodes of pancreatitis. It is documented in most cases with FCS due to the mutations of key proteins in lipolysis, including LPL, APOC2, APOA5, LMF1 and GPIHBP1. CASE PRESENTATION: We report the successful management of a 35-year-old pregnant woman carrying a novel homozygous frameshift mutation c.48_49insGCGG (p.P17A fs*22) in the GPIHBP1 gene with previous severe episodes of acute pancreatitis triggered by pregnancy, resulting in adverse obstetrical outcomes. With careful monitoring, the patient underwent an uneventful pregnancy and delivered a baby with no anomalies. CONCLUSIONS: The case report contributes to the understanding of GPIHBP1-deficient familial chylomicronemia syndrome (FCS) and highlights gestational management of FCS patient.

Molecular analysis of three known and one novel LPL variants in patients with type I hyperlipoproteinemia.

BACKGROUND AND AIMS: Type I hyperlipoproteinemia, also known as familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disorder caused by variants in LPL, APOC2, APOA5, LMF1 or GPIHBP1 genes. The aim of this study was to identify novel variants in the LPL gene causing lipoprotein lipase deficiency and to understand the molecular mechanisms. METHODS AND RESULTS: A total of 3 individuals with severe hypertriglyceridemia and recurrent pancreatitis were selected from the Lipid Clinic at Sahlgrenska University Hospital and LPL was sequenced. In vitro experiments were performed in human embryonic kidney 293T/17 (HEK293T/17) cells transiently transfected with wild type or mutant LPL plasmids. Cell lysates and media were used to analyze LPL synthesis and secretion. Media were used to measure LPL activity. Patient 1 was compound heterozygous for three known variants: c.337T > C (W113R), c.644G > A (G215E) and c.1211T > G (M404R); patient 2 was heterozygous for the known variant c.658A > C (S220R) while patient 3 was homozygous for a novel variant in the exon 5 c.679G > T (V227F). All the LPL variants identified were loss-of-function variants and resulted in a substantial reduction in the secretion of LPL protein. CONCLUSION: We characterized at the molecular level three known and one novel LPL variants causing type I hyperlipoproteinemia showing that all these variants are pathogenic.

Familial Chylomicronemia Syndrome: A Clinical Guide For Endocrinologists.

OBJECTIVE: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by mutations in lipoprotein lipase, resulting in accumulation of chylomicrons in plasma and hypertriglyceridemia. Elevated triglycerides cause several complications in patients, the most serious being episodes of acute pancreatitis. This review focuses on expert guidance and opinion from an experienced lipidologist and endocrinologist as well as a current review of the literature, as there are no specific guidelines on FCS. METHODS: Discussion of expert guidance and opinion review of current literature. RESULTS: To date, there is no pharmacologic treatment for affected patients, and management options primarily include adoption of an extremely restricted, very-low-fat diet, along with avoidance of certain medications and alcohol. Endocrinologists often diagnose and manage patients with metabolic disorders, including patients with high triglyceride levels, but rare diseases like FCS can be missed or poorly evaluated due to knowledge gaps about disease state. Given endocrinologists' role in the treatment of lipid disorders, it is important that they understand the clinical signs and symptoms of FCS to correctly diagnose patients. Patients with FCS can be identified based on a defined clinical criteria and a thorough review of medical history, after excluding differential diagnoses and secondary factors. Typical manifestations include hypertriglyceridemia characterized by lipemic serum, history of abdominal pain, and acute/recurrent pancreatitis. Secondary factors to be excluded are pregnancy, alcohol abuse, uncontrolled diabetes, and use of certain medications. CONCLUSION: FCS is a rare, inherited lipid disorder disease that often goes underdiagnosed and unmanaged. This review provides a summary of clinical characteristics of FCS that can be potentially used to screen patients in an endocrinologist's office and direct them to the appropriate standard of care. ABBREVIATIONS: apoB = apolipoprotein B; apoC-III = apolipoprotein CIII; ASO = antisense oligonucleotide; FCS = familial chylomicronemia syndrome; HTG = hypertriglyceridemia; LPL = lipoprotein lipase; LPLD = lipoprotein lipase deficiency.

Prognosis of Patients With Familial Hypercholesterolemia After Acute Coronary Syndromes.

BACKGROUND: Patients with heterozygous familial hypercholesterolemia (FH) and coronary heart disease have high mortality rates. However, in an era of high-dose statin prescription after acute coronary syndrome (ACS), the risk of recurrent coronary and cardiovascular events associated with FH might be mitigated. We compared coronary event rates between patients with and without FH after ACS. METHODS: We studied 4534 patients with ACS enrolled in a multicenter, prospective cohort study in Switzerland between 2009 and 2013 who were individually screened for FH on the basis of clinical criteria according to 3 definitions: the American Heart Association definition, the Simon Broome definition, and the Dutch Lipid Clinic definition. We used Cox proportional models to assess the 1-year risk of first recurrent coronary events defined as coronary death or myocardial infarction and adjusted for age, sex, body mass index, smoking, hypertension, diabetes mellitus, existing cardiovascular disease, high-dose statin at discharge, attendance at cardiac rehabilitation, and the GRACE (Global Registry of Acute Coronary Events) risk score for severity of ACS. RESULTS: At the 1-year follow-up, 153 patients (3.4%) had died, including 104 (2.3%) of fatal myocardial infarction. A further 113 patients (2.5%) experienced nonfatal myocardial infarction. The prevalence of FH was 2.5% with the American Heart Association definition, 5.5% with the Simon Broome definition, and 1.6% with the Dutch Lipid Clinic definition. Compared with patients without FH, the risk of coronary event recurrence after ACS was similar in patients with FH in unadjusted analyses, although patients with FH were >10 years younger. However, after multivariable adjustment including age, the risk was greater in patients with FH than without, with an adjusted hazard ratio of 2.46 (95% confidence interval, 1.07-5.65; P=0.034) for the American Heart Association definition, 2.73 (95% confidence interval, 1.46-5.11; P=0.002) for the Simon Broome definition, and 3.53 (95% confidence interval, 1.26-9.94; P=0.017) for the Dutch Lipid Clinic definition. Depending on which clinical definition of FH was used, between 94.5% and 99.1% of patients with FH were discharged on statins and between 74.0% and 82.3% on high-dose statins. CONCLUSIONS: Patients with FH and ACS have a >2-fold adjusted risk of coronary event recurrence within the first year after discharge than patients without FH despite the widespread use of high-intensity statins.

Non-accidental Trauma Work-up: Unusual Retinal Finding Leads to a Rare Diagnosis.

Lipoprotein lipase (LPL) deficiency is an autosomal recessive condition due to absent or decreased activity of LPL enzyme. The LPL deficiency is a rare condition that is mainly diagnosed in children, but there is no standard screening method at this time. In our report, we describe a 6-day-old male infant who was found to have hypertriglyceridemia after lipemia retinalis was diagnosed from a fundoscopic examination for nonaccidental trauma work-up. After dietary modification was done, his triglyceride levels decreased significantly, and there were no complications. When diagnosed later in life, recurrent pancreatitis can be a significant complication.

Clinical, biochemical and molecular analysis of two infants with familial chylomicronemia syndrome.

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disease due mainly to inherited deficiencies in the proteins or enzymes involved in the clearance of triglycerides from circulation. It usually happens in late childhood and adolescence, which can have serious consequences if misdiagnosed or untreated. In the present study, we investigated two Chinese male babies (A and B), 30d and 48d in age, respectively, who have milky plasma. Clinical, biochemical, and radiological assessments were performed, while samples from the patients were referred for molecular diagnosis, including genetic testing and subsequent analysis of related genes. The fasting serum lipids of the two patients showed extreme lipid abnormalities. Through a low-lipid formula diet including skimmed milk and dietary advice, their plasma lipid levels were significantly lower and more stable at the time of hospital discharge. The genetic testing revealed compound heterozygote mutations in the lipoprotein lipase (LPL) gene for patient A and two known compound heterozygote LPL gene mutations for the patient B. FCS is the most dramatic example of severe hypertriglyceridemia. Early diagnosis and timely dietary intervention is very important for affected children.

Lipoprotein lipase deficiency: clinical, biochemical and molecular characteristics in three patients with novel mutations in the LPL gene.

Lipoprotein lipase (LPL) deficiency, caused by mutations in the LPL gene, is a rare autosomal recessive disorder manifesting in early childhood with recurrent abdominal pain, hepatosplenomegaly, acute pancreatitis, lipaemia retinalis and eruptive xanthomas. Typical laboratory findings are lactescent serum, extreme hypertriglyceridaemia and hypercholesterolaemia. The diagnostics is based on postheparin serum LPL assay and DNA analyses of the LPL gene. We report clinical, biochemical and molecular data of three children with LPL deficiency. One child manifested since the first week of life with recurrent abdominal pain (Patient 1), the second with abdominal distension and hepatosplenomegaly since the second month of life (Patient 3) and patient 2, asymptomatic younger brother of patient 1, was diagnosed in the first week of life. Lipaemia retinalis and splenomegaly were present in two symptomatic children, hepatomegaly in patient 3 and acute pancreatitis in patient 1. All children had lactescent serum, profound hypertriglyceridaemia (124 ± 25 mmol/l; controls < 2.2), hypercholesterolaemia (22.8 ± 7.3 mmol/l, controls < 4.2) and their LPL immunoreactive mass in serum did not increase after heparin injection. Molecular analyses revealed that both siblings are homozygous for novel mutation c.476C > G in the LPL gene changing the conserved amino acid of the catalytic centre. The third patient is a compound heterozygote for mutations c.604G>A and c.698A>G in the LPL gene, both affecting highly conserved amino acids. We conclude that LPL deficiency must be considered in neonates and young infants with abdominal pain and hypertriglyceridaemia because early treatment might prevent development of life-threatening acute pancreatitis.

Familial chylomicronemia syndrome related chronic pancreatitis: a single-center study.

BACKGROUND: Hypertriglyceridemia induces acute recurrent pancreatitis, but its role in the etiology of chronic pancreatitis (CP) is controversial. This study aimed to evaluate the clinical, laboratory and radiological findings of 7 patients with CP due to type 1 hyperlipidemia compared to CP patients with other or undefined etiological factors. METHODS: We retrospectively analyzed the clinical, laboratory and radiological findings of 7 CP patients with type 1 hyperlipidemia compared to CP patients without hypertriglyceridemia. These 7 patients had multiple episodes of acute pancreatitis and had features of CP on abdominal CT, endoscopic retrograde cholangiopancreatography and/or endoscopic ultrasonography. RESULTS: All CP patients were classified into two groups: a group with type 1 hyperlipidemia (n=7) and a group with other etiologies (n=58). The mean triglyceride level was 2323+/-894 mg/dL in the first group. Age at the diagnosis of CP in the first group was significantly younger than that in the second group (16.5+/-5.9 vs 48.3+/-13.5, P<0.001). The number of episodes of acute pancreatitis in the first group was significantly higher than that in the second group (15.0+/-6.8 vs 4.0+/-4.6, P=0.011). The number of splenic vein thrombosis in the first group was significantly higher than that in the second group (4/7 vs 9/58, P=0.025). Logistic regression analysis found that younger age was an independent predictor of CP due to hypertriglyceridemia (r=0.418, P=0.000). CONCLUSIONS: Type 1 hyperlipidemia appears to be an etiological factor even for a minority of patients with CP. It manifests at a younger age, and the course of the disease might be severe.

Validation of the familial chylomicronaemia syndrome (FCS) score in an ethnically diverse cohort from UK FCS registry: Implications for diagnosis and differentiation from multifactorial chylomicronaemia syndrome (MCS).

BACKGROUND AND AIMS: Prognosis and management differ between familial chylomicronaemia syndrome (FCS), a rare autosomal recessive disorder, and multifactorial chylomicronaemia syndrome (MCS) or severe mixed hyperlipidaemia. A clinical scoring tool to differentiate these conditions has been devised but not been validated in other populations. The objective of this study was to validate this score in the UK population and identify any additional factors that might improve it. METHODS: A retrospective validation study was conducted using data from 151 patients comprising 75 FCS and 76 MCS patients. All participants had undergone genetic testing for genes implicated in FCS. Validation was performed by standard methods. Additional variables were identified from clinical data by logistic regression analysis. RESULTS: At the recommended FCS score threshold ≥10 points, the sensitivity and specificity of the score in the UK population were 96% and 75%, respectively. The receiver operating characteristic (ROC) curve analysis yielded an area under the curve (AUC) of 0.88 (95% CI 0.83-0.94, p < 0.001). This study identified non-European (predominantly South Asian) ethnicity, parental consanguinity, body mass index (BMI) < 25 kg/m2, and recurrent pancreatitis as additional positive predictors, while BMI >30 kg/m2 was found to be a negative predictor for FCS. However, inclusion of additional FCS predictors had no significant impact on performance of standard FCS score. CONCLUSIONS: Our study validates the FCS score in the UK population to distinguish FCS from MCS. While additional FCS predictors were identified, they did not improve further the score diagnostic performance.