Lipoprotein Lipase Deficiency Research Articles

Abstract 13168: Total Lipoprotein Lipase Deficiency Does Not Impact Atherosclerosis Development in Low Density Lipoprotein Receptor Deficient Mice

Introduction: Elevated LDL cholesterol (LDL-C) is a major causal factor for CVD. However, the importance of elevated triglyceride rich lipoproteins (TRLs) on CVD is still being investigated. Lipoprotein lipase (LpL) is the rate limiting enzyme hydrolyzing circulating very low density lipoprotein (VLDL) and chylomicrons. The effect of increased TRLs as an independent factor on atherosclerosis is not known, in part, because hypertriglyceridemia associates with low levels of LDL-C. Objective: We tested whether whole body LpL deficiency in mice combined with LDL receptor (LDLR) deficiency and an atherogenic diet affects lesion formation. Hypothesis: LpL deficient mice will not show increased atherosclerosis progression as compared to control mice, despite severe dyslipidemia, due to reduced infiltration of atherogenic lipids into the aortic endothelium. Methods: Induced global LpL deficiency (i Lpl -/- ) was created by tamoxifen injection to activate beta actin-driven cre. To knock down hepatic LDLR we utilized anti sense oligonucleotides (ASOs) as well as a PCSK9 expressing AAV. Results: i Lpl -/- mice on chow diet have elevated plasma triglycerides, increased VLDL cholesterol, lower LDL-C and lower high density lipoprotein cholesterol (HDL-C) compared to control Lpl fl/fl mice. However, when hepatic LDLR was knocked down with using LDLR ASO or AAV PCSK9, iLpl -/- mice displayed elevated LDL-C of about 150 mg/dl, similar to the levels seen in control mice with LDLR knockdown. When i Lpl -/- mice were fed an atherogenic Western diet for 16 weeks, i Lpl -/- mice developed severe hypertriglyceridemia (1500-8000 mg/dl) and increased total cholesterol to ~1500 mg/dl. LDL-C levels were similar to those of control mice with LDLR knockdown; ~200 mg/dl. HDL-C was lower in i Lpl -/- mice compared to the controls (~10 mg/dl vs ~30 mg/dl). i Lpl -/- mice had slightly smaller lesions in brachiocephalic arteries but macrophage content was similar to the controls. Aortic root lesion size was similar in both groups of mice. Conclusion: Despite severe hypertriglyceridemia, hypercholesterolemia and low HDL-C, iLpL -/- mice did not exhibit altered atherosclerosis progression, likely because of the absence of LpL-derived atherogenic lipids or remnant lipoproteins.

A Modern Approach to Dyslipidemia.

Lipid disorders involving derangements in serum cholesterol, triglycerides, or both are commonly encountered in clinical practice and often have implications for cardiovascular risk and overall health. Recent advances in knowledge, recommendations, and treatment options have necessitated an updated approach to these disorders. Older classification schemes have outlived their usefulness, yielding to an approach based on the primary lipid disturbance identified on a routine lipid panel as a practical starting point. Although monogenic dyslipidemias exist and are important to identify, most individuals with lipid disorders have polygenic predisposition, often in the context of secondary factors such as obesity and type 2 diabetes. With regard to cardiovascular disease, elevated low-density lipoprotein cholesterol is essentially causal, and clinical practice guidelines worldwide have recommended treatment thresholds and targets for this variable. Furthermore, recent studies have established elevated triglycerides as a cardiovascular risk factor, whereas depressed high-density lipoprotein cholesterol now appears less contributory than was previously believed. An updated approach to diagnosis and risk assessment may include measurement of secondary lipid variables such as apolipoprotein B and lipoprotein(a), together with selective use of genetic testing to diagnose rare monogenic dyslipidemias such as familial hypercholesterolemia or familial chylomicronemia syndrome. The ongoing development of new agents—especially antisense RNA and monoclonal antibodies—targeting dyslipidemias will provide additional management options, which in turn motivates discussion on how best to incorporate them into current treatment algorithms.

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.

Clinical Management of Hypertriglyceridemia in the Prevention of Cardiovascular Disease and Pancreatitis.

Purpose of ReviewHypertriglyceridemia (HTG) is common and is a significant contributor to atherosclerosis and pancreatitis risk. Specific HTG treatments have had variable success in reducing atherosclerosis risk. Novel therapies for severe HTG treatment and pancreatitis risk reduction are likely to be available soon. These novel therapies are expected to have broader applications for more moderate HTG and atherosclerosis risk reduction as well.Recent FindingsNHANES 2012 data has confirmed a reduction in average triglyceride (TG) levels in the US population. Dietary modification and weight reduction when needed remain the core treatment elements for all individuals with HTG, while statin therapy is a foundational pharmacologic care for atherosclerotic cardiovascular disease (ASCVD) event risk reduction. In addition, the REDUCE-IT study provides evidence for additional benefit from the use of high-dose icosapent ethyl (IPE) on top of background medical therapy in adults with moderate HTG and ASCVD or type 2 diabetes mellitus (T2D) and additional ASCVD risk factors. However, treatment with eicosapentaenoic acid (EPA) combined with docosahexanoic acid (DHA) did not reduce ASCVD in a similar population studied in the STRENGTH trial. Furthermore, novel therapeutics targeting PPAR-ɑ, as well as ApoC-III and AngPTL3, effectively lower TG levels in individuals with moderate and severe HTG, respectively. These treatments may have applicability for reducing risk from ASCVD among individuals with chylomicronemia; in addition, ApoC-III and AngPTL3 treatments may have a role in treating individuals with the rare monogenic familial chylomicronemia syndrome (FCS) at risk for acute pancreatitis (AP).SummaryResidual ASCVD risk in individuals treated with contemporary care may be due in part to non-LDL lipid abnormalities including HTG. The findings from REDUCE-IT, but not STRENGTH, confirm that consumption of high-dose EPA may reduce ASCVD risk, while combination therapy of EPA plus DHA does not reduce ASCVD in a similar population. TG lowering likely reduces ASCVD risk in individuals with HTG, but ASCVD risk is multifactorial; the added benefit of IPE to contemporary preventive therapy is the consequence of differential non-TG biologic properties between the two fatty acids. Acute pancreatitis is more difficult to study prospectively since it is less common; however, TG lowering is likely critical for the care of at-risk individuals. Additional benefit from novel therapy that has an impact on this otherwise refractory condition is anticipated.

Genomic testing in patients with suspected Familial Chylomicronaemia Syndrome (FCS) and evaluation of the FCS clinical scoring tool: Presented by Natalie Forrester in place of Julie Evans

Genomic testing in patients with suspected Familial Chylomicronaemia Syndrome (FCS) and evaluation of the FCS clinical scoring tool: Presented by Natalie Forrester in place of Julie Evans

Development of a novel PRO instrument for use in familial chylomicronemia syndrome

BackgroundFamilial chylomicronemia syndrome (FCS), a rare genetic disorder characterized by high levels of circulating triglycerides, negatively impacts multiple organs, including the liver and pancreas.ObjectiveThe objective of this study was to develop and support the content validity of a novel patient-reported outcome (PRO) measure addressing FCS symptoms and impacts. To facilitate use in clinical trials of new treatments, evidence supporting the new measure needed to be consistent with regulatory guidance and requirements.MethodsA pool of items addressing symptoms and impacts of FCS was initially developed based on data from a large burden-of-illness study with patients with FCS as well as a review of available literature and existing PRO measures. Two rounds of qualitative interviews were conducted with patients with FCS (N = 10) to refine the draft items and support the measure’s content validity. Each interview began with concept elicitation followed by cognitive debriefing of the draft FCS measure.ResultsPatient-reported symptoms and impacts of FCS were generally consistent with those identified by the burden-of-illness study; abdominal pain was particularly prevalent and salient for patients. Suggested changes to the draft item pool were generally minor. Comprehensibility and ease of completion for the final instrument were confirmed during the second set of interviews.ConclusionThe content validity of the final 17-item FCS Symptoms and Impacts Scale is strongly supported by patient input gathered through both a large burden-of-illness study and qualitative research. To further support use in clinical trials, psychometric evaluation of the measure is underway.

Symptoms and impacts of familial chylomicronemia syndrome (FCS): A qualitative study and development of a patient-centered conceptual model

Background and Aims: Familial chylomicronemia syndrome (FCS) is a rare, hereditary, metabolic disorder. FCS causes high levels of triglycerides in the blood, which can lead to abdominal pain, fatty deposits under the skin, and acute pancreatitis (AP). Management of FCS relies on adherence to a very low-fat diet. We aimed to understand the symptoms of FCS and their impact on health-related quality of life (HRQoL).

PROMIS® measures capture extensive pain interference associated with familial chylomicronemia syndrome

Background and Aims: Familial Chylomicronemia Syndrome (FCS) is a rare genetic disorder that often entails life-disrupting abdominal pain. Legacy measures have not been sensitive to FCS’s pain impact. We assessed the ability of PROMIS® pain measures to detect and describe pain in FCS.

Effectiveness and safety of lomitapide in a patient with familial chylomicronemia syndrome

Background and Aims: Familial chylomicronemia syndrome (FCS) is characterized by severe fasting hypertriglyceridemia, abdominal pain and recurrent acute pancreatitis. Available triglyceride-lowering drugs are insufficient to avoid pancreatitis.Therefore, there is a significant unmet medical need for effective triglyceride-lowering drugs for patients with FCS.

Hypertriglyceridemia and acute pancreatitis complicated by splenic and hepatic infarcts

Background and Aims: Hypertriglyceridemia is a common clinical problem that can be exacerbated by numerous medications and medical conditions. Primary hypertriglyceridemia caused by lipoprotein lipase (LPL) deficiency is an extremely rare metabolic disorder. LPL is a lipolytic enzyme involved in catalyzing hydrolysis of triglycerides (TG) and very low-density lipoprotein (VLDL) particles.

Two novel mutations of the LPL gene in two Chinese family cases with familial chylomicronemia syndrome

The aim of this study was to investigate the clinical features and genetic causes of two family cases with familial chylomicronemia syndrome (FCS). Clinical manifestations of proband 1 and her families, and also proband 2 showed severe hypertriglyceridemia, especially the triglycerides levels of two probands were extremely high. Gene sequencing results showed that the LPL genes in each of the two probands had a new mutation site. For the proband 1, a compound heterozygous mutation at c.429 (c.429 + 1G > T) was detected in the LPL gene, which was splicing mutation and inherited from her mother. Homozygous mutation was detected in the LPL gene of proband 2, the nucleotide mutation at c.802 (c.802C > T) exhibited missense mutation, his parents and brother had a heterozygous mutation at the same site. It was confirmed that the conservative lipoprotein lipase superfamily domain changed an amino acid from histidine to tyrosine at p. 268 (p. His268Tyr). Flow cytometry confirmed the deficient expression of LPL protein in two families. These results indicated that the mutation in LPL gene might be the cause of familial chylomicronemia syndrome.

A Case of Glycogen Storage Disease Type 1a Mimicking Familial Chylomicronemia Syndrome.

Glycogen storage disease type 1a (GSD1a) is an autosomal recessively inherited inborn error of metabolism caused by a mutation in the G6PC gene, which encodes the catalytic subunit of glucose-6-phosphatase-α (G6Pase-α) enzyme. This enzyme plays a role in the final step of gluconeogenesis and glycogenolysis. Patients carrying GSD1a show growth retardation, hypoglycemia, hepatomegaly, hepatic steatosis, hyperlipidemia, hyperuricemia and lactic acidemia. Long-term symptoms include gouty arthritis and uric acid stones, osteoporosis, renal failure, intestinal impairment, cirrhosis and hepatic adenomas, and eventually, hepatocellular carcinoma. Hyperlipidemia is the indicator of poor metabolic control in GSD1a. Patients with variable levels of triglycerides (TGs) have been reported in the literature. We present a case of GSD1a that presented with severe hypertriglyceridemia (HTG) mimicking familial chylomicronemia syndrome.

Volanesorsen for treatment of familial chylomicronemia syndrome

ABSTRACT Introduction Familial chylomicronemia syndrome (FCS) is a rare subtype of severe hypertriglyceridemia that affects ~1 in 100, 000 to 1,000,000 individuals. The major risk to health is acute pancreatitis. FCS is defined by biallelic loss-of-function mutations in one of five canonical genes that encode proteins critical to lipolysis of large triglyceride-rich lipoprotein particles. Unlike the vast majority of patients with severe hypertriglyceridemia, FCS patients lack any lipolytic capacity and are thus resistant to standard medications. Areas covered This review focuses on a mechanism that effectively reduces elevated triglyceride levels in FCS, namely interference of synthesis of apolipoprotein (apo) C-III. Volanesorsen is an antisense RNA drug administered subcutaneously that knocks down apo C-III, resulting in dramatic reductions in triglyceride levels both in FCS patients and in the wider population of subjects with severe hypertriglyceridemia. Expert opinion Volanesorsen is a highly effective treatment to reduce elevated triglycerides in FCS patients, providing proof-of-concept of the validity of targeting apo C-III. However, off target effects of volanesorsen, including thrombocytopenia, may ultimately limit its use. Nonetheless, building on the knowledge derived from the volanesorsen experience, there is intensified interest in promising newer agents that also target apo C-III but have technical modifications that limit potential off target adverse effects.

Serum HDL-C values: An extremely useful marker for differentiating homozygous lipoprotein lipase deficiency from severe hypertriglyceridemia with other causes in Japan: A meta-analysis based on literatures on Japanese homozygous lipoprotein lipase deficiency

Backgrounds and aimLipoprotein lipase (LPL) deficiency is a genetic disorder with a defective gene for lipoprotein lipase, leading to very high triglycerides. In the daily practice it is much more common to come across severely hypertriglyceridemia without homozygous or compound heterozygous LPL deficiency (SHTG). MethodsWe investigated on how to screen homozygous or compound heterozygous LPL deficiency using lipid parameters by meta-analyzing past 20 subjects on this genetic disease reported by Japanese investigators. As a comparison with LPL deficiency, 21 subjects with SHTG from recent two studies were included in this study. ResultsSerum HDL-C levels were significantly lower in LPL deficiency than in SHTG (0.38 ± 0.13 vs 0.94 ± 0.28 mmol/L (mean ± SD), p < 0.001), whereas other serum lipids did not differ between the two groups. The ROC curve ± standard error for serum HDL-C for discriminating the two groups was 0.97 ± 0.019. Sensitivity and specificity for distinguishing the two groups were 90% and 95%, respectively when serum HDL-C 0.62 mmol/L was adopted as cut point. ConclusionWe found for the first time that serum HDL-C is an extremely useful marker for discriminating LPL deficiency from SHTG in Japanese population.

Eruptive xanthoma model reveals endothelial cells internalize and metabolize chylomicrons, leading to extravascular triglyceride accumulation.

Although tissue uptake of fatty acids from chylomicrons is primarily via lipoprotein lipase (LpL) hydrolysis of triglycerides (TGs), studies of patients with genetic LpL deficiency suggest additional pathways deliver dietary lipids to tissues. Despite an intact endothelial cell (EC) barrier, hyperchylomicronemic patients accumulate chylomicron-derived lipids within skin macrophages, leading to the clinical finding eruptive xanthomas. We explored whether an LpL-independent pathway exists for transfer of circulating lipids across the EC barrier. We found that LpL-deficient mice had a marked increase in aortic EC lipid droplets before and after a fat gavage. Cultured ECs internalized chylomicrons, which were hydrolyzed within lysosomes. The products of this hydrolysis fueled lipid droplet biogenesis in ECs and triggered lipid accumulation in cocultured macrophages. EC chylomicron uptake was inhibited by competition with HDL and knockdown of the scavenger receptor-BI (SR-BI). In vivo, SR-BI knockdown reduced TG accumulation in aortic ECs and skin macrophages of LpL-deficient mice. Thus, ECs internalize chylomicrons, metabolize them in lysosomes, and either store or release their lipids. This latter process may allow accumulation of TGs within skin macrophages and illustrates a pathway that might be responsible for creation of eruptive xanthomas.

Rare Variants in Triglycerides-Related Genes Increase Pancreatitis Risk in Multifactorial Chylomicronemia Syndrome.

Severe hypertriglyceridemia (fasting triglycerides [TG] concentration ≥10 mmol/L) can be caused by multifactorial chylomicronemia syndrome (MCS) or familial chylomicronemia syndrome (FCS). Both conditions are associated with an increased risk of acute pancreatitis. The clinical differences between MCS patients with or without a rare variant in TG-related genes have never been studied. To compare the clinical and biochemical characteristics of FCS, positive-MCS patients, and negative-MCS patients, as well as to investigate the predictors of acute pancreatitis in MCS patients. All patients referred at the clinic for severe hypertriglyceridemia underwent genetic testing for the 5 canonical genes involved in TG metabolism (LPL, APOC2, GPIHBP1, APOA5, and LMF1) using next-generation sequencing. A total of 53 variant negative-MCS, 22 variant positive-MCS and 28 FCS subjects were included in this retrospective cross-sectional study. A significant difference was observed in the prevalence of pancreatitis (9%, 41%, and 61%) and multiple pancreatitis (6%, 23%, and 46%) in the negative-MCS, the positive-MCS, and the FCS groups, respectively (P < 0.0001). Predictors of pancreatitis among MCS subjects included the presence of a rare variant, lower apolipoprotein B, as well as higher gamma-glutamyl transferase, maximal TG value, and fructose consumption. We observed that the MCS individuals who carried a rare variant have an intermediate phenotype between FCS and negative-MCS subjects. Since novel molecules such as the antisense oligonucleotide against APOC3 mRNA showed high efficacy in reducing TG levels in patients with multifactorial chylomicronemia, identification of higher-risk MCS patients who would benefit from additional treatment is essential.

Pregnancy in Familial Chylomicronemia Syndrome: Plasmapheresis as Therapeutic Approach

Introduction: Familial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive disease where functional loss of lipoprotein lipase results in severe hypertriglyceridemia. Patients often experience recurrent acute pancreatitis, a life-threatening disease. Serum triglycerides (TGs) are physiologically elevated several folds during pregnancy, which especially endanger patients with FCS to develop hypertriglyceridemic pancreatitis (HP) and complications like miscarriage. Despite the development of new drugs for FCS, their safety in pregnancy has not yet been confirmed and their treatment represents a big challenge. Clinical Case: A 30-year women was hospitalized for planned reevaluation while 22 weeks pregnant. She was diagnosed with FCS at the age of one month with failure to thrive, jaundice and lipemic blood serum (homozygous for the LPL gene variation C.1019-2A>T). During childhood she was treated with low-fat diet with average TG levels 10–15 mmol/l (n<1,7 mmol/l). In the past five years, she was hospitalized for HP five times due to loss of compliance to diet (serum TGs > 30 mmol/l). The last episode of HP was provoked by pregnancy and resulted in miscarriage. At the admission, the patient was asymptomatic, with BMI:18,5 kg/m2, TGs: 32,2 mmol/l (n<1,7 nmol/l), lipase: 21 U/L (n<60 U/L). Gynecology status and child growth parameters were normal. Due to inability to achieve lower TG levels plasmapheresis was started two times per week. The overall mean of pre plasmapheresis values of TGs were 21,68 nmol/l (ranging from 15,9 to 26,3 nmol/l) and post plasmapheresis were 7,15 mmol/L (ranging from 4,9 to 9,9 mmol/l). Due to the frequent need for plasmapheresis and high risk pregnancy, the patient was transferred to the Gynecology department. The patient had no adverse reactions and fetal monitoring was performed before, during and after procedure with no abnormalities registered. Plasmapheresis was performed using Spectra OPTIA via peripheral veins with 5% albumin replacement, proceeded by 250-500ml of 0.9% saline infusion. At 40th gestational week Cesarean section was performed and a healthy baby boy (weight: 3540 g, lenght: 49 cm) was born with Apgar score 10/10. We followed baby boy the first five years of the childhood. So far the patient has not experienced HP and the baby boy has normal levels of TGs. Conclusion: Our case showed a succesfull pregnancy outcome in female patient with FCS achieved by multidisciplinary approach including plasmapheresis. For the first time therapeutic plasmaferesis was used in order to prevent pancreatitis and potential complications for both mother and child.

Tratamiento de la quilomicronemia

Fasting chylomicronaemia appears in type V (multifactorial chylomicronaemia syndrome, MCS), and in type I (familial chylomicronaemia syndrome, FCS). MCS needs to be treated as in any general hypertriglyceridaemia: low-calorie diet, avoid sugar and alcohol, reduce body weight, control of diabetes and, in some cases, common lipid lowering-drugs, such as fibrates or omega-3 fatty acids.For type I HLP, FCS, patients should adhere to a strict very low fat diet, usually less than 15-20 g per day. In spite of this, many patients with FCS suffer from recurrent abdominal pain and/or acute pancreatitis. Volanesorsen, an antisense oligonucleotide against apolipoprotein C-III, is the only drug approved to control the disease. As shown in the APPROACH study, the administration of volanesorsen at a weekly dose of 285 mg induced at three month a reduction of triglycerides of 77% (primary end-point) and a reduction of 1712 mg/dL from the baseline. Among patient receiving volanesorsen, 77% reached a fasting triglyceride value below 750 mg/dL. The most frequent side effects were a skin reaction at injection site and low platelet levels, which should be monitored.

Metabolismo de los triglicéridos y clasificación de las hipertrigliceridemias

Triglycerides (TG) are the most important molecules for the energy reserve of our body. After their hepatic or intestinal synthesis from fatty acids, they are carried by chylomicrons (QM (intestinal origin) or VLDL (hepatic origin) in plasma. Their catabolism is determined by the action of the lipoprotein lipase protein complex (LPL) and the hepatic receptors (RLDL and LRP-1) are responsible for their clearance are. Changes in the production or catabolism leads to hypertriglyceridaemia (HTG). The HTG are classified according to severity as, mild-moderate (150-885mg/dl), severe (>885mg/dl), or very severe (>1770mg/dl). They can be primary and secondary depending on origin. In the main primary form is highlighted Familial Chylomicronaemia Syndrome (CFS), a very severe form due to mutations in the LPL gene or associated proteins. Most HTG are due to a combination of genetic and environmental predisposing factors.

Management strategy and novel ophthalmological findings in neonatal severe hypertriglyceridemia: a case report and literature review

BackgroundNeonatal severe hypertriglyceridemia is rarely reported in the literature and there is no consensus for hypertriglyceridemia management at this age group.MethodsThe index case is a 4-week-old male infant with severe hypertriglyceridemia accidentally discovered during a circumcision surgery. His clinical and genetic characteristics and his successful management strategy are described. Furthermore, a detailed ophthalmological examination of the proband was conducted at 3 and 6 months of age using Fourier-domain-optical coherence tomography.ResultsTriglycerides level at presentation was extremely high 33,727 mg/dL (380.8 mmol/L). Two sessions of exchange blood transfusion on two consecutive days successfully reduced triglycerides to 382 mg/dL (4.3 mmol/L) with no adverse effects. The infant was discharged 3 days later. At discharge, the mother was advised to continue breastfeeding together with a medium-chain triglycerides formula. Satisfactory growth parameters and lipid profile values were obtained for a follow-up duration of 5 months with no reported attacks of acute pancreatitis. Lipoprotein lipase deficiency was confirmed by the detection of the LPL homozygous pathogenic variant c.805G > A; p.(Glu269Lys). Early corneal and macular lesions were detected and persisted on follow-up despite relatively good lipemic control.ConclusionThis case highlights the importance of the early discovery of severe hypertriglyceridemia during the neonatal period, which is needed for prompt management and prevention of severe complications. Rationalized breastfeeding can be tolerated within the diet plan of the disease with satisfactory outcomes. To our knowledge, it is the first study reporting early corneal and macular affection by severe hypertriglyceridemia in a neonate. Prolonged follow-up is needed to determine the extent of ophthalmological lesions.