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

BACKGROUND: Neonatal severe hypertriglyceridemia is rarely reported in the literature and there is no consensus for hypertriglyceridemia management at this age group. METHODS: The 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. RESULTS: Triglycerides 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. CONCLUSION: This 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.

[Primary hyperchylomicronemia].

Primary hyperchylomicronemia is characterized by a marked hypertriglyceridemia due to an increase in chylomicrons, which may cause acute pancreatitis and eruptive xanthomas. This entity includes familial lipoprotein lipase (LPL) deficiency, familial apolipoprotein C-II deficiency, primary type V hyperlipoproteinemia, and idiopathic hyperchylomicronemia. Idiopathic hyperchylomicronemia is caused by an LPL inhibitor or autoantibody against LPL. More recently, patients with primary hyperchylomicronemia caused by mutations in the gene for glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1(GPIHBP1) or lipase maturation factor 1(LMF1). For the treatment of primary hyperchylomicronemia, a strict restriction of dietary fat is essential to avoid acute pancreatitis.

Familial hypertriglyceridaemia and type 2 diabetes in pregnancy: prevention of acute pancreatitis with diet control and omega-3 fatty acids.

Acute pancreatitis in pregnancy is rare and can be caused by hypertriglyceridaemia. The management of hypertriglyceridaemia in pregnancy is complex and challenging as many lipid-lowering medications have been found to be unsafe in pregnancy. Patients who present with hypertriglyceridaemia commonly have multiple risk factors such as, diabetes, alcohol excess and hypothyroidism which pose a greater challenge to the management of these patients. We present a case of a 31-year-old woman presenting with familial hypertriglyceridaemia and type 2 diabetes mellitus in her third pregnancy. She had an uneventful pregnancy with the use of omega-3 fatty acids nutritional support, low-fat diet and tight glucose control with insulin and metformin.

Clinical Practice Recommendations for Pediatric Dyslipidemia.

The leading cause of mortality in the United States is atherosclerotic cardiovascular disease (ASCVD). Atherosclerotic lesions begin during childhood and can place individuals at greater risk for ASCVD. Providers play an active role in preventing the progression of risk factors and future ASCVD events through appropriate clinical management of genetic and acquired dyslipidemias in the pediatric population. Health care providers need to be aware of current recommendations related to screening for dyslipidemia, lifestyle modification strategies, pharmacologic treatment, and guidelines for ongoing monitoring. Most patients with mild to moderate dyslipidemia can be managed by a primary care provider. It is imperative that providers understand the pathophysiology, screening methods, and available treatment options to effectively manage the condition. Frequent reassessment of family history and adherence to lifestyle modifications and pharmacologic interventions is essential for effective treatment.

Monogenic pediatric dyslipidemias: classification, genetics and clinical spectrum.

Monogenic disorders that cause abnormal levels of plasma cholesterol and triglycerides have received much attention due to their role in metabolic dysfunction and cardiovascular disease. While these disorders often present clinically during adulthood, some present most commonly in the pediatric population and can have serious consequences if misdiagnosed or untreated. This review provides an overview of monogenic lipid disorders that present with unusually high or low levels of plasma cholesterol and/or triglycerides during infancy, childhood and adolescence. Biochemical and genetic findings, clinical presentation and treatment options are discussed with an emphasis upon recent advances in our understanding and management of these monogenic disorders.

A-IMilano apoprotein. Decreased high density lipoprotein cholesterol levels with significant lipoprotein modifications and without clinical atherosclerosis in an Italian family.

Significant hypertriglyceridemia with a very marked decrease of high density lipoproteins (HDL)-cholesterol levels (7-14 mg/dl) was detected in three members (father, son, and daughter) of an Italian family. The three affected individuals did not show any clinical signs of atherosclerosis, nor was the atherosclerotic disease significantly present in the family. Lipoprotein lipase and lecithin:cholesterol acyltransferase activites were normal or slightly reduced. Morphological and compositional studies of HDL in the subjects showed a significant enlargement of the lipoprotein particles (approximately 120 vs. approximately 94 A for control HDL) and a concomitant increase in the triglyceride content. Analytical isoelectric focusing of HDL apoproteins provided evidence for multiple isoproteins in the apoprotein(apo)-A-I range, with nine different bands being detected instead of the usual four bands observed in normal subjects. Two-dimensional immunoelectrophoresis against apo-A antiserum indicated a clear reduction of apo-A in the alpha electrophoretic region, with splitting of the protein "peak." The observation in otherwise clinically healthy subjects of hypertriglyceridemia, reduced HDL-cholesterol, and marked apoprotein abnormalities, without a significant incidence of atherosclerotic disease in the family suggests this is a new disease entity in the field of lipoprotein pathology, very probably related to an altered amino acid composition of the apo-A-I protein (see Weisgraber et al. 1980. J. Clin. Invest. 66: 901-907).

Chewing the Fat: A Case Report of Therapeutic Plasma Exchange in Hypertriglyceridemia-Induced Pancreatitis.

Hypertriglyceridemia is the third most common etiology of acute pancreatitis, but lacks a clear, evidence-based treatment approach. We present the case of a 25-year-old man who was admitted eleven times over seven years for hypertriglyceridemia-induced pancreatitis. In his first ten admissions, he received conservative therapy. During his eleventh admission, he underwent therapeutic plasma exchange with lowering of serum triglycerides from 5080 to 332 mg/dL. He was discharged on hospital day five and was noted to have persistently lowered triglyceride levels upon follow up. The case affirms plasma exchange's ability to rapidly lower serum triglyceride levels and provides future research opportunities for examining the long-term effects of this treatment.

Type IV hyperlipoproteinemia: effects of a caloric restricted type IV diet versus physical training plus isocaloric type IV diet.

Serum lipids, plasma insulin and glucagon, aerobic capacity, and body composition were examined in middle-aged men (X age = 44.2 years) with type IV hyperlipoproteinemia to determine the relative effectiveness of a caloric restricted type IV hyperlipoproteinemia diet (group A) versus physical training plus an isocaloric type IV diet (group B). After 9 weeks of the above interventions, reductions (P less than 0.01) in mean cholesterol levels from 213 to 186 (12% change) and from 205 to 185 mg/dl (9% change), and in triglyceride levels from 332 to 211 (29% change) and from 263 to 138 mg/dl (42% change) were found for groups A and B, respectively. A small reduction in mean fasting insulin level was found only in group B; this reduction appeared inversely associated with increases in aerobic capacity in group B (r = -0.66). Both interventions were without effect on fasting glucagon levels. The physical training program prescribed resulted in a 12% increase in aerobic capacity (group B). Significant mean body weight reductions of 7.7 lb (P less than 0.01) and 2.9 lb (P less than 0.01) were seen for groups A and B, respectively; these absolute body weight reductions differed significantly (P less than 0.05) between groups. Both groups significantly lost body fatness (P less than 0.01). These reductions in body weight and body fatness appeared independent of changes in lipid levels. These results demonstrate that both interventions reduce serum lipids in men with type IV hyperlipoproteinemia but that physical training plus an isocaloric type IV diet may be the more advantageous of the two regimens, since a greater percentage decrease and a more sustained reduction in serum triglyceride levels, and a greater reduction of fasting hyperinsulinemia were observed in group B.

Pronounced lipoprotein lipid reduction obtained by combined lipid-lowering treatment in patients with atherosclerotic disease.

The feasibility of reducing serum lipoprotein levels in patients with atherosclerotic disease by combining diet, clofibrate and nicotinic acid (niceritrol) has been investigated. An additive lipid-lowering effect of diet and the two drugs was demonstrated. It was possible to reduce the serum triglycerides (TG) in hypertriglyceridaemic patients by 50-60%. This corresponded to a reduction of very low density lipoprotein (VLDL) TG by 73 and 66% in patients with hyperlipoproteinaemia (HLP) type IIB and IV, respectively. In normotriglyceridaemic patients the serum TG concentration decreased by 30-40%. The serum cholesterol (Chol) concentration was reduced by 33% and the low density lipoprotein (LDL) Chol by 37% in HLP type IIA and IIB. The LDL Chol decreased by 32% in normolipoproteinaemic patients and by 21% in HLP type IV. The mean value for serum cholesterol after therapy was in all groups close to 200 mg/100 ml. In hypertriglyceridaemic patients high density lipoprotein (HDL) Chol increased by 18%. Clofibrate and niceritrol differed with regard to the effect on serum lipoprotein concentrations as well as on other metabolic parameters. Niceritrol was significantly more effective than clofibrate in lowering LDL Chol and in increasing HDL Chol. Niceritrol treatment significantly reduced the Chol/TG ratio in VLDL while no such effect was seen during clofibrate administration. The two drugs also showed significantly different effects on the fractional removal rate (K2) of triglyceride-rich lipoproteins as measured by the intravenous fat tolerance test (IVFTT). The K2 was significantly increased by clofibrate but was not affected by niceritrol treatment. The two drugs differed also with regard to the effects on serum uric acid concentration and the liver function tests. The plasma fibrinogen levels and the erythrocyte sedimentation rates were reduced during treatment with both niceritrol and clofibrate. The present study demonstrates that it is possible to obtain substantial reductions of serum lipoprotein concentrations by combining lipid-lowering diet, clofibrate and niceritrol treatment. There was an additive lipid-lowering effect of this treatment and the combination of the two drugs seemed beneficial in regard to certain possible side effects. The impact of a lipid reduction within this range on cardiovascular morbidity and mortality remains to be evaluated.

Variations in lipids and proteins of lipoproteins by fenofibrate in some hyperlipoproteinaemic states.

A total of 28 hyperlipoproteinaemic patients (8 type IIA, 12 type IIB and 8 type IV) were studied. Each patient was put on a 'prudent' isocaloric diet (50% carbohydrate, 30% fat, 20% protein) following a 2-month period of wash-out. Fenofibrate (300 mg/day) was then given for 2 periods of 2 months, each separated by a 2-month period in which only the dietary treatment was continued. Fenofibrate induced a significantly beneficial effect on the abnormal plasma levels of lipids and apolipoproteins A-I and B in all three phenotypes. Total cholesterol significantly decreased in type IIA and IIB; total triglycerides decreased significantly in all three types. HDL-C increased in all the patients but significantly only in those presenting types IIB and IV. ApoB significantly decreased in the 3 groups while apoA-I increased. The ratio apoA/apoB increased significantly in the three groups. Enzymatic parameters did not vary during the drug treatment. However, 6 patients (16%) dropped out because of gastro-intestinal side effects.

Effect of low dose supplementation of L-carnitine on lipid metabolism in hemodialyzed children.

Long-term intravenous supplementation with low dose L-carnitine (5 mg/kg body wt) was investigated in seven hemodialyzed children with type IV hyperlipoproteinemia. Carnitine was given at the completion of each hemodialysis treatment (3 times a week) over a period of five months. This treatment resulted in a rise in total plasma carnitine concentrations (117.7 +/- 33.0 microM) as compared to before therapy (37.9 +/- 15.8 microM); the free fraction was the chief portion of this elevation. Prior to therapy the patients had high plasma triglyceride concentrations (3.82 +/- 1.6 mM) which were markedly reduced after five months of carnitine therapy (1.86 +/- 0.7 mM; P less than or equal to 0.05). The initially low HDL-cholesterol levels (0.91 +/- 0.2 mM) were increased (1.13 +/- 0.2 mM; P less than or equal to 0.05) after supplementation. Thus, long-term low-dose carnitine supplementation improves the disturbed lipid metabolism; this suggests an important role for carnitine in uremic children and may justify the use of supplemental carnitine.

Chylomicronemia syndrome. Interaction of genetic and acquired hypertriglyceridemia.

Chylomicrons accumulating in plasma obtained after an overnight fast are always abnormal and can be detected in association with triglyceride levels above 1000 mg per dl. The chylomicronemia syndrome is associated with marked hypertriglyceridemia (plasma triglyceride level above 2000 mg per dl), abdominal pain or pancreatitis, eruptive xanthomata, lipemia retinalis, dyspnea, mental aberrations, and other minor findings. The marked hypertriglyceridemia is usually due to the interaction of a common familial form of hypertriglyceridemia and a common acquired form of hypertriglyceridemia secondary to another disease, drug, or alcohol. Rarely, genetic abnormalities in lipoprotein lipase are the cause of the marked hypertriglyceridemia. Therapy that successfully lowers plasma triglyceride levels is associated with clearing of the symptoms and signs of the chylomicronemia syndrome and prevention of its recurrence.

Cardiovascular risk in patients with treated familial hypercholesterolaemia and patients with severe hypertriglyceridaemia.

A study was performed to determine the morbidity and mortality from ischaemic heart disease (IHD) in patients with heterozygous familial hypercholesterolaemia (FH) and severe hypertriglyceridaemia (pretreatment plasma triglyceride greater than 5 mmol/l). Twenty-nine (38%) of 76 patients with FH and 8(44%) of 18 patients with hypertriglyceridaemia had evidence of IHD. Over a mean follow-up period of 5.5 years, 2 patients with hypertriglyceridaemia died but there were no deaths in patients with FH. This contrasts with earlier reports which showed a high mortality in FH patients. The lower mortality may be due to improved treatment and consequent lower levels of cholesterol.

Hypertriglyceridemia in a 5-day-old newborn--a case report.

Neonatal hypertriglyceridaemia is extremely rare in pediatrics. We narrowed down the possibilities to a case of lipoprotein lipase (LPL) deficiency through a designed process of elimination with this particular patient. The biochemical hallmark of the disease is the presence of hyperchylomicronemia in fasting plasma. The patient responded well to a special formula containing median chain triglyceride (MCT). This was one of the youngest cases of hyperlipidemia and hyperlipoproteinemia to be reported during the neonatal period. Therefore the approach is mainly through the process of elimination because of inadequate laboratory facilities.

[Correction of hypercholesterolemia and dyslipoproteinemia by plasmapheresis in patients with stenocardia resistant to drug therapy]. / Korrektsiia giperkholesterinemii i dislipoproteidemii metodom plazmafereza u bol'nykn so stenokardiei, rezistentnoi k medikamentoznoi terapii.

Plasmapheresis was used to correct blood lipid composition in patients with angina at rest and angina of effort (functional classes 3-4). In addition to a drop in total cholesterol and triglycerides, cholesterol in low and very-low-density lipoproteins fell abruptly, while high-density-lipoprotein cholesterol, on the contrary, increased considerably. Clinical improvement of the patients was also recorded.

[Effect of partial ileoshunting on hyperlipoproteinemia in patients with atherosclerosis]. / Vliianie chastichnogo ileoshuntirovaniia na giperlipoproteidemiiu u bol'nykh aterosklerozom.

In 57 atherosclerotic patients with concomitant hyperlipoproteinemia operations of partial ileoshunts were performed consisting in shunting the distal third of the small intestine. The follow-up observation was up to 6 years. A persistent decrease of the elevated level of lipids and cholesterol of atherogenic LDL and VLDL was noted as well as a considerable and stable increase of the level of cholesterol of antiatherogenic very high density lipoproteins and a lower atherogeneity coefficient. It facilitates stabilization and regression of atherosclerosis.