Effect of Continuous LDL Apheresis with Dextran-Sulfate Cellulose Column System on a Child with Homozygous Familial Hypercholesterolemia

A new system for selective low density lipoprotein apheresis with an automated regenerating column using dextran-sulfate (DS) as ligand was evaluated for six months in a 13-year-old boy homozygous for familial hypercholesterolemia. Two columns each containing 150 ml of DS cellulose were alternately used after rinsing with a regenerating solution. The patient could well tolerate the volume in the system. The values of plasma total cholesterol decreased by 79.4 ± 4.9% of the pretreatment levels after a total of 5ℓ plasma apheresis, while those of high density lipoprotein cholesterol did not change. Although the values of CH₅₀ decreased, no adverse reaction was seen during the period of treatment. It was concluded that the present apheresis system was highly efficacious and safe for children homozygous for the mutant LDL receptor gene.     

Squalene and noncholesterol sterols in serum and lipoproteins of children with and without familial hypercholesterolemia

Squalene and noncholesterol sterols, e.g. lathosterol and plant sterols, the respective markers of cholesterol synthesis and absorption, are transported with cholesterol in serum lipoproteins. Their concentrations and ratios to cholesterol in serum and lipoproteins have not been carefully compared, especially in children and in marked hypercholesterolemia. Thus, we measured these variables with gas-liquid chromatography in 18 children with and 29 without familial hypercholesterolemia, all aged 5-17 y. Concentrations of most noncholesterol sterols were higher in serum, LDL, and intermediate density lipoprotein in the children with than those without familial hypercholesterolemia. Despite accumulation of noncholesterol sterols mainly in LDL (75% in familial hypercholesterolemia and 55% in non-familial hypercholesterolemia, p < 0.001), their ratios were mostly similar in serum and lipoproteins of the two groups. The ratios of squalene and lathosterol were higher in VLDL and intermediate density lipoprotein, whereas in LDL that of lathosterol was lower than the respective serum values in both groups. Absorption marker sterol ratios were highest in HDL in both groups. Thus, even though the ratios of noncholesterol sterols to cholesterol in serum reflect, in general, synthesis and absorption of cholesterol, their ratios in different lipoproteins could give additional information of cholesterol metabolism.     

Low-density lipoprotein apheresis in a patient aged 3.5 years

A 3.5 y‐old girl carrying a severe mutation of the LDL‐receptor gene known as “FH Pavia”, affected by homozygous familial hypercholesterolemia (FH), and at high risk of developing coronary artery atherosclerosis was treated with selective dextran sulphate cellulose (DSC) column low‐density lipoprotein apheresis (LDL‐a). This is the youngest patient ever treated with LDL‐a. Plasma total cholesterol (982 mg/dl) and LDL‐cholesterol (939mg/dl) (T‐Chol, LDL‐Chol) levels at baseline showed a transient decrease: –13.4%, and –16.8%, respectively, after 9 mo of combined treatment with a diet, cholestyramine (max. 12g/d) and atorvastatin (max. 30mg/d). However, the drugs were discontinued because of intolerance and an increase in aminotransferases and creatine phosphokinase in the plasma. Moreover, after 9 mo of this therapy, the mean plasma T‐Chol and LDL‐Chol levels were still high (930 mg/dl and 869.5 mg/dl, respectively). Therefore, 9 consecutive treatments with LDL‐a were carried out every 15 d (plasma volumes treated: 1000–1700 ml). Mean plasma T‐Chol, LDL‐Chol, triglycerides (TG), and Lp(a) decreased significantly: –75.5%, –77.2%, –67.5% and ?50.8%, respectively. HDL‐cholesterol (HDL‐Chol) concentration was considerably decreased immediately after apheresis because of haemodilution (X: ?45.1%). Conclusion: LDL‐a treatment improved the plasma apo B 100‐containing lipoproteins–LDL, Lp(a)‐profile in a homozygote with a severe inherited disorder in which coronary artery atherosclerosis frequently has its clinical onset before 10 y of age. At the time of this report, no significant side effects had been observed.     

Lovastatin therapy in receptor-negative homozygous familial hypercholesterolemia: lack of effect on low-density lipoprotein concentrations or turnover

To determine whether at least part of the fall in low density lipoprotein (LDL) levels during lovastatin therapy might be the result of a reduced secretion of lipoproteins by the liver, three children 6 to 9 years of age with receptor-negative homozygous familial hypercholesterolemia underwent treatment with lovastatin. These patients have no capacity to synthesize LDL receptors. During lovastatin therapy, at a dose of 2 mg/kg/day, there was no decrease in LDL-cholesterol levels, nor was the turnover rate of LDL affected by the drug. The only significant change was a 74% drop in very low-density lipoprotein during treatment. We conclude that lovastatin is not effective in treatment of receptor-negative homozygous familial hypercholesterolemia. The most likely mechanism of action for this drug is to increase LDL receptor activity.     

Long-term treatment of severe familial hypercholesterolemia in children: effect of sitosterol and bezafibrate.

Seven prepubertal children (age range 5.3 to 10.8 years) with severe heterozygous familial hypercholesterolemia (serum cholesterol concentration 416 +/- 85 mg/dL and low-density lipoprotein [LDL] cholesterol concentration 360 +/- 90 mg/dL) were first treated by dietary intervention, second by sitosterol (3 x 2 g/d), and third by bezafibrate (2 x 200 mg/d). Each treatment period lasted 3 months. Subsequently, a treatment combining half the dose of sitosterol and bezafibrate was administered for the following 24 months. Diet alone reduced total and LDL cholesterol values by 4.5% (not significant) and 6.6% (P less than .05), respectively. Sitosterol lowered total and LDL cholesterol values by 17% (P less than .05) when compared with diet alone. Compared with sitosterol, bezafibrate produced a more pronounced effect on total and LDL cholesterol values (-18% and -28%, P less than .05), and high-density lipoprotein cholesterol concentration increased significantly from 48 mg/dL to 55 mg/dL. Combined treatment with half the dose each of sitosterol and bezafibrate was as effective as the higher dose of bezafibrate, and reduction averaged almost 40% and 50% for total and LDL cholesterol values; this lipid-lowering effect persisted for the next 24 months. Laboratory safety parameters and physical examination revealed no obvious side effects. This study indicates that the combination of sitosterol (3 x 1 g/d) plus bezafibrate (1 x 200 mg/d) is an alternate, acceptable, safe, and effective therapeutic approach for treatment of severe hypercholesterolemia in children with high-risk familial hypercholesterolemia.     

Preemptive liver transplantation in a child with familial hypercholesterolemia

Maiorana A, Nobili V, Calandra S, Francalanci P, Bernabei S, El Hachem M, Monti L, Gennari F, Torre G, de Ville de Goyet J, Bartuli A. Preemptive liver transplantation in a child with familial hypercholesterolemia.
Pediatr Transplantation 2011: 15:E25–E29. © 2010 John Wiley & Sons A/S. Abstract: Familial hypercholesterolemia is an autosomal codominant disorder associated with markedly elevated plasma concentration of LDL‐cholesterol and increased cardiovascular risk. Homozygous patients have rapid development of atherosclerosis with death from cardiovascular disease even in childhood. Life‐long recurrent apheresis to reduce plasma LDL‐cholesterol is considered the gold standard for treatment. Liver transplantation can be curative for this condition, but is usually only considered after the development of cardiovascular disease. We report a 5.5‐yr‐old child initially misdiagnosed with heterozygous familial hypercholesterolemia and treated by low‐fat diet only. In view of persistent hypercholesterolemia and development of xanthomatosis, new molecular studies indicated the presence of two different mutations in the LDL receptor gene, with one being a deletion of two exons not identifiable with standard sequencing analysis. Recurrent plasma apheresis in combination with statins lowered, but did not normalize plasma LDL‐cholesterol levels. It caused progressive reduction of the size of xanthomas and prevented the development of vascular complications. After two yr, liver transplantation normalized LDL‐cholesterol levels and completely resolved the skin lesions. Preemptive liver transplantation is a definitive cure of familial homozygous hypercholesterolemia and might be more effective if performed before development of vascular complications.     

THE FATTY ACID COMPOSITION OF SERUM LOW DENSITY LIPOPROTEIN- AND LYMPHOCYTE CHOLESTEROL ESTERS IN CHILDREN WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA

Abstract. Andersen, G. E. and Johansen, K. B. (The Neonatal Department, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark). Fatty acid composition of serum low density lipoprotein- and lymphocyte cholesterol esters in children with heterozygous familial hypercholesterolemia. Acta Paediatr Scand, 69:453, 1980.—The content of free and esterified cholesterolin serum low density lipoprotein (LDL) was measured in 19 children with heterozygous familial hypercholesterolemia (FH) and in 10 normal siblings. In FH both free and esterified cholesterol were found to be elevated. Furthermore the fatty acid composition of serum LDL- and lymphocyte cholesterol esters was determined. However, no difference was found between FH heterozygotes and normals thus indicating that LDL-hypocatabolism typically found in FH does not correlate with an abnormal fatty acid composition of LDL-cholesterol esters nor with an impaired cholesterol esterification intracellularly in lymphocytes.     

Low-density lipoprotein plasmaphaeresis with and without lovastatin in the treatment of the homozygous form of familial hypercholesterolaemia

A 7-year-old girl with homozygous familial hypercholesterolaemia and plasma low-density lipoprotein (LDL)-cholesterol levels of 820 mg/dl (21.2 mmol/l) and progressive xanthomata was treated with heparin extracorporeal low-density lipoprotein precipitation (HELP) to lower her plasma LDL. On weekly HELP treatment she maintained her pre-HELP treatment LDL-cholesterol levels at 409 mg/dl (10.6 mmol/l). The long-term HELP treatment was well tolerated and led to regression of her xanthomata. Subsequently, lovastatin [Mevacor; Merck Sharp & Dohme, Westpoint, Pa., USA (20 mg/day)] was added to the regimen, causing a further 20% decrease in her pre-HELP treatment plasma LDL-cholesterol levels. Lovastatin alone did not sufficiently lower her plasma LDL and could not replace the weekly HELP therapy. Our data show that lovastatin is an effective adjunctive therapy for lowering plasma LDL-cholesterol in a homozygous patient, once plasma LDL levels have already been lowered by regular HELP treatment.This work is dedicated to Professor Fritz Scheler, Department of Internal Medicine, University of Göttingen, on his 65th birthday     

Family study in familial hypercholesterolemia with a receptor-negative homozygous 9-year-old boy

A 2-year-old boy showed massive xanthomas, especially tendon xanthomas and cutaneous xanthomas on the knees. When presented to us at the age of 9 years, his total cholesterol was 700-1100 mg/dl, LDL-cholesterol 600-1000 mg/dl, and triglycerides were normal, which is the constellation of hyperlipoproteinemia type IIa. LDL receptor studies showed 3% of normal binding activity, which defines the receptor-negative form of homozygous familial hypercholesterolemia (FH). Remarkably there was no sign of coronary heart disease in angiography. Three great-grandparents and the paternal grandfather (at 44 years) died from cardiovascular disease. The maternal grandmother is heterozygote for FH as well as three siblings of the father. In all family members we determined apolipoprotein B, apo-E-phenotype and the lipoprotein fraction Lp (a). In this family there seems to be no genetic coupling between the LDL receptor gene and the gene for Lp (a).- Therapy of heterozygous FH should start as early as possible, before symptoms appear. Therefore pediatricians should be very critical about the cholesterol values of their little patients.     

Long-term prevention of premature coronary atherosclerosis in homozygous familial hypercholesterolemia

Homozygous familial hypercholesterolemia (FHH) leads to severe premature atherosclerosis. A 22-year-old woman with FHH has been treated with a combination of H.E.L.P. apheresis (heparin-mediated extracorporeal LDL precipitation) and statins for 15 years. The combined treatment maintained a plasma LDL-cholesterol reduction from baseline of 840 to 122 mg/dL (85% reduction). In addition, H.E.L.P. apheresis reduced the elevated lipoprotein(a) and fibrinogen levels by 60% to 70%. All xanthomata disappeared. There is no evidence of premature atherosclerosis studied by means of electron beam computed tomography and (13)N-ammonia positron emission tomography: The entire coronary vasculature is free of calcifications. Her myocardial blood flow at rest (87 mL/100 g/min) and during stress (308 mL/100 g/min) and the coronary flow reserve (3.5) are normal after H.E.L.P. treatment. This case demonstrates the efficacy and safety of the combined treatment of H.E.L.P. apheresis and statins even in serious cases of FHH.     

Diagnosis and management of familial dyslipoproteinemia in children and adolescents

CAD results from atherosclerosis, a chronic disease process that has its origin in childhood. Children and adolescents can be at higher risk for CAD by virtue of being from families with premature CAD or familial dyslipoproteinemias. The plasma lipid and lipoprotein levels result from a number of complex metabolic processes that are under the control of genetic and environmental (e.g., diet) influences. The normal ranges of plasma lipids and lipoproteins in children are known, and children and adolescents with dyslipoproteinemia are ordinarily defined as those having levels of plasma total, LDL, or triglyceride above the 95th percentile or with a low HDL cholesterol below the 5th percentile. Children of a parent with documented dyslipoproteinemia or with family history of premature CAD may be screened in the fasting state any time after 2 years of age. Following the exclusion of secondary causes of dyslipoproteinemia, the diagnosis of primary dyslipoproteinemia can be made. Lipoprotein patterns are not diagnostic for a given genotype. Efforts to determine further the biochemical defects responsible for a given phenotype have led to the investigation of gene coding for the apolipoproteins, the key enzymes in the lipoproteins pathways (LPL, HDL, and LCAT) and the receptors that process lipoproteins, such as the LDL receptor and the chylomicron remnant receptor. From a practical standpoint, the diagnosis of the kind of dyslipoproteinemia in a child will depend upon the nature and severity of the dyslipoproteinemia, both in the child (or adolescent) and in parents and siblings. Marked increases in plasma total and LDL cholesterol in the child and in at least one of the parents often reflect the presence of familial hypercholesterolemia, an inherited dominant condition due to a defect in the LDL receptor gene. The triglyceride levels are often normal. If the child has a different dyslipoproteinemia pattern from siblings and parents, then the diagnosis of familial combined hyperlipidemia or hyperapobetalipoproteinemia should be considered. Most children with mild or borderline elevations in total and LDL cholesterol will have polygenic hypercholesterolemia. Triglyceride problems in children and adolescents are relatively uncommon, particularly the more severe hypertriglyceridemia such as that found in lipoprotein lipase and apoC-II deficiency, dysbetalipoproteinemia, and type V hyperlipoproteinemia. High levels of Lp(a) lipoprotein, in isolation or in combination with other dyslipoproteinemia, accelerate risk for CAD. Low levels of HDL cholesterol in the absence of other abnormalities suggest the diagnosis of hypoalphalipoproteinemia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Lipid and lipoprotein profiles in children with familial hypercholesterolaemia: effects of therapy

In 71 children with familial hypercholesterolaemia the effect of dietary and/or medical treatment was evaluated. Initial total cholesterol and low density lipoprotein (LDL)-cholesterol levels were significantly lower in children who were consecutively treated by diet (Step-One-Diet) than in those who received additional medication. By dietary treatment, the median total cholesterol level (236.5 mg/dl; range 210–510 mg/dl) was reduced by 7.4% and the median LDL-cholesterol level (162 mg/dl; range 126–423 mg/dl) by 9.9%. By dietary and medical therapy, the median total cholesterol level (330 mg/dl; range 270–424 mg/dl) was reduced by 29.7% and the median LDL-cholesterol level (263 mg/dl; 192–333 mg/dl) by 25.9%. High density lipoprotein (HDL)-cholesterol and HDL 3 remained unchanged. HDL 2 showed a significant decrease of 15.6% up to 27 mg/dl (13–42 mg/dl) on medical treatment. Apolipoprotein A I levels did not change during therapy. Initial apolipoprotein B levels were significantly higher in children who were treated by diet and medication and were reduced by 28.9% by combined therapy. In 28 patients (39.4%) an excess of lipoprotein (a) was detected. Regarding the apolipoprotein E phenotype, 32.2% of the patients carried the risk gene ɛ4 in a hetero- or homozygous form. Conclusion Early dietary and/or medical treatment in hypercholesterolaemic children significantly ameliorates the lipoprotein status. The pretherapy lipoprotein status seems to prognosticate the effectiveness of therapy. Received: 16 April 1997 / Accepted in revised form: 27 May 1998     

Correlation of lipid profiles and anthropometric variables with serum lipoprotein(a) levels in childhood

The aim of the present study was to evaluate lipoprotein(a) distribution in children and to assess its association with lipid profile and anthropometric variables. We studied 98 children (44 girls and 54 boys) with ages ranging from 6 to 7 years, who were included in an epidemiological study on the prevalence of hypercholesterolemia in children in the province of Biscay. The following parameters were determined: weight and height, body mass index, lipoprotein(a), and lipid profile. Lipid profile included total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, apolipoprotein B, and apolipoprotein A1. The mean and median serum lipoprotein(a) levels were 13.07 and 5.56 mg/dl respectively and were 11.43 and 3.92 mg/dl for boys and 15.09 and 8.32 mg/dl for girls. Lipoprotein(a) concentrations > 30 mg/dl were found in 7.4% of the boys and in 11.4% of the girls. The mean values and prevalences of lipoprotein(a) > 30 mg/dl were lower in boys than in girls but these differences were not statistically significant. A positive correlation was found between lipid profile (LDL-cholesterol, apolipoprotein B and LDL-cholesterol/HDL-cholesterol index) and lipoprotein(a) levels. When evaluating anthropometric variables, we found a statistically significant inverse correlation between weight and lipoprotein(a). In view of the cumulative effect of cardiovascular risk factors and the results of this study, we believe that lipoprotein(a) determination should be considered in children with an unfavorable lipid profile.     

The levels of asymmetric dimethylarginine, homocysteine and carotid intima-media thickness in hypercholesterolemic children

The aim of this study was to examine the intima-media thickness (IMT) of carotid arteries and endothelial function parameters such as plasma asymmetric dimethylarginine (ADMA) and homocysteine levels in hypercholesterolemic children and to investigate the relations of these parameters with hypercholesterolemia. Fifty-seven hypercholesterolemic and 37 healthy children were included in the study. Hypercholesterolemia was defined as 155 mg/dl and above for low-density lipoprotein (LDL)-cholesterol. Plasma concentrations of ADMA and homocysteine were measured and the measurement of carotid IMT was determined. Both carotid IMT and plasma ADMA levels were significantly higher in hypercholesterolemic children than healthy children (p<0.01). No significant difference was determined in homocysteine concentration between hypercholesterolemic children and the control group (p>0.05). No significant correlation was observed between lipid profiles and the levels of ADMA and homocysteine. However, a significant positive correlation was found between carotid IMT and total and LDL-cholesterol levels and between the levels of ADMA and LDL-cholesterol. In conclusion, the progressive increase in ADMA levels and carotid IMT and the positive relationship between carotid IMT and serum cholesterol levels support that plasma ADMA levels and carotid IMT can be indicators of early atherosclerosis in hypercholesterolemic children.     

Pediatric familial type II hyperlipoproteinemia: therapy with diet and colestipol resin.

Effects of a low-cholesterol, polyunsaturate-rich diet and a synthetic organic bile sequestrant polymer (U26,597A, colestipol) were studied in 21 children, heterozygous for familial hypercholesterolemia. Total cholesterol, beta-lipoprotein cholesterol, and triglyceride were measured twice on habitual diet, monthly for six months on a low-cholesterol diet, and monthly for six months on low-cholesterol diet plus 10 gm of colestipol per day. Total cholesterol (mean +/- 1 SD) was 295 +/- 37 on habitual diet, 278 +/- 29 on low-cholesterol diet, and fell significantly to 242 +/- 29 mg/100 ml on diet plus colestipol. Low-density lipoprotein (LDL) cholesterol was 234 +/- 37 on habitual diet, 220 +/- 28 on low-cholesterol diet, and fell significantly to 179 +/- 26 mg/100 ml on diet plus drug. Plasma triglyceride levels on habitual diet were 79 +/- 31, remained unchanged on low-cholesterol diet, 86 +/- 22, and were unaffected by low-cholesterol diet plus drug, 85 +/- 17 mg/100 ml. On diet alone, plasma LDL was not normalized (less than 170 mg/100 ml) in any of the 21 children, and cholesterol fell to within normal limits (less than 230 mg/100 ml) in only one child. The combination of diet plus colestipol resin normalized total and LDL cholesterol in 52% of the children. Cholesterol was lowered to a "moderately elevated" range of 230 to 250 mg/100 ml in an additional 14% of the children and LDL was lowered to a range of 170 to 190 mg/100 ml in an additional 29%. In 33% of the children, cholesterol remained greater than 250 mg/100 ml despite diet plus colestipol, while LDL was greater than 190 mg/100 ml in 19%. Colestipol is an effective and well-tolerated cholesterol lowering compound which, in conjunction with diet, may prove to be very useful in the treatment of children heterozygous for familial hypercholesterolemia.     

The child as proband. High prevalence of unrecognized and untreated hyperlipidemia in parents of hyperlipidemic children

The authors evaluated the lipids of parents of hypercholesterolemic children to assess the prevalence of unrecognized and/or untreated hyperlipidemia. Biologic parents of 34 children had measurements of total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (n = 47) or total cholesterol only (n = 14). Lipid abnormalities were defined according to guidelines established by the National Cholesterol Education Program. Abnormal values were defined as total cholesterol greater than 240 mg/dl, low-density lipoprotein (LDL) cholesterol greater than 160 mg/dl, HDL cholesterol less than 35 mg/dl, and triglycerides greater than 250 mg/dl. Borderline values were defined as total cholesterol between 200 and 240 mg/dl and LDL cholesterol between 130 and 160 mg/dl. Abnormal values were found in 32/61 (52%) and borderline values were found in 12/61 (20%) parents. Of the abnormal parents, 13/32 (41%) had unrecognized or known but untreated hyperlipidemia, and 9/12 (75%) of the borderline parents had unrecognized abnormalities. In all families where both parents were tested, at least 1 had a lipid abnormality. The authors conclude that when children with hypercholesterolemia are identified, parents should also have lipids assessed. Treatment programs for children should also be directed at the parents.     

Biliary bile acid composition of the human fetus in early gestation

The study was designed to investigate the hyperlipidaemia associated with the steroid responsive nephrotic syndrome in children and in particular to examine the mechanism for the delayed clearance of the circulating triglyceride-rich lipoproteins. The possibility that plasma from patients with steroid responsive nephrotic syndrome may contain an inhibitor of lipoprotein lipase activity was studied by examining the effect of the addition of plasma from patients, on normal postheparin lipoprotein lipase activity. Plasma from children with steroid responsive nephrotic syndrome significantly inhibited lipoprotein lipase activity (p less than 0.001), whereas that from patients with familial hypercholesterolaemia and normal children had no significant effect. The inhibition of lipoprotein lipase activity by plasma from patients with steroid responsive nephrotic syndrome correlated significantly with their increased plasma cholesterol and reduced plasma albumin concentrations (p less than 0.001 and less than 0.02, respectively), but there was no significant correlation with plasma triglyceride concentrations. Thus, the degree of inhibition probably reflected the severity of the condition at the time of study. Neither the cholesterol, albumin nor triglyceride concentrations appeared to directly influence the lipoprotein lipase activity of postheparin plasma.     

Usefulness of serum apolipoprotein B levels for screening children with primary dyslipoproteinemias.

OBJECTIVE--To assess the use of serum apolipoprotein B levels for screening children with primary dyslipoproteinemia (those with elevated levels of low-density lipoprotein cholesterol [LDL-C]) and to know the types of dyslipoproteinemias we can identify. DESIGN--Criterion standard. SETTING--Referral center. PARTICIPANTS--We have studied 267 children. Of these, 31 had parents with dyslipoproteinemia, 38 had parents with ischemic heart disease, and 43 had hypercholesterolemia detected by routine analyses. One hundred fifty-five were considered healthy children and comprised the control group. INTERVENTIONS--None. MEASUREMENTS AND MAIN RESULTS--Sensitivity was 87% for total serum cholesterol levels and 73% for serum apolipoprotein B levels. Of the children studied, 31 had elevated levels of serum LDL-C. The types of dyslipoproteinemia in children with both elevated levels of serum LDL-C and apolipoprotein B consisted of heterozygous familial hypercholesterolemia, found in 12 (50%) of 24 patients; familial combined hyperlipidemia, found in 11 (46%) of 24 patients; and polygenic hypercholesterolemia, found in one (4%) of 24 patients. CONCLUSIONS--Serum apolipoprotein B level appears to be a good tool for screening children with elevated levels of LDL-C and is equivalent to using total serum cholesterol levels. In children with elevated serum LDL-C and apolipoprotein B levels, we can identify not only patients with heterozygous familial hypercholesterolemia but also those with familial combined hyperlipidemia or polygenic hypercholesterolemia.     

Cardiovascular risk factors m relation to the serum concentrations of copper and zinc: epidemiological study on children and adolescents in the Spanish province of Navarra

This investigation was carried out to show the possible association between groups of children with extreme values of copper and zinc concentrations and cardiovascular risk indicators. Serum copper and zinc concentrations were analysed in a group of 3887 children from Navarra, Spain (both sexes, aged 4–17 years). Hypertension, unfavourable serum lipid profile (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, and cholesterol/HDL and LDL/HDL ratios), and degree of adiposity (weight, height, subcutaneous skinfolds, Quetelet's index and mean of subcutaneous skinfolds) were evaluated. Positive correlation was found between several lipid parameters and copper and zinc concentrations, i.e. degree of correlation related with age, except for copper/HDL and triglycerides/zinc ratios, where correlation remained negative at all points. Copper levels were correlated with adiposity parameters in an age-dependent fashion (Quetelet's index: r = 0.01 forages 4–7 years to r = 0.10, p < 0.01 for ages 14–17 years; mean skinfold thickness: r = 0.05 for ages 4–7 years up to r = 0.18, p < 0.01 for ages 14–17 years). Most correlations between lipid parameters and copper and zinc are markedly amplified if adiposity parameters are taken into account. However, the only significant association was the established relation between high copper concentrations (> x + 2SD) and unfavourable serum lipid profile (LDL/HDL > 2.2).     

Concentration of plasma beta-carotene in cystic fibrosis children with pancreatic insufficiency

Patients with cystic fibrosis (CF) have significantly decreased plasma concentrations of antioxidant vitamins which is considered to result both from fat malabsorption and from chronic pulmonary infection. The aim of this study was to investigate levels of vitamin A and beta-carotene in plasma of CF subjects with pancreatic exocrine insufficiency. In thirty CF patients mean plasma concentrations of vitamin A (1.17 micromol/l) was lower by 30% and that of beta-carotene (1.3 micromol/l) by 60% than in healthy children. Vitamin A level was positively correlated with beta-carotene (r=0.67; p<0.001). Ratios of beta-carotene to total cholesterol and cholesterol of LDL (low density lipoprotein) were 40% lower than in the control group. We conclude that in our CF patients the concentration of beta-carotene does not seem to be sufficient to inhibit lipid peroxidation especially of LDL fraction.