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PO3-79 UNIQUE CLINICAL PHENOTYPE IN A YOUNG BOY WITH TYPE I HYPERLIPOPROTEINEMIA ASSOCIATED WITH A COMBINED MUTATION ON THE LIPOPROTEIN LIPASE GENE
Poster Sessions PO3 Pathophysiology of lipids and lipoproteins lipoproteins and integrates these to form a dynamic lipoprotein profile. The model can incorporate experimental data from different analytical measurements. Several hypotheses on the mechanism of lipoprotein delipidation were incorporated into the model, and tested for their ability to reproduce the observed lipoprotein profiles. In conclusion: Particle Profiler provides new insight into lipoprotein delipidation based on lipoprotein profile data. PO3-78
FAMILIAL HYPOBETALIPOPROTEINEMIA DUE TO APOLIPOPROTEIN B GENE MUTATIONS CAUSES INTESTINAL FAT ACCUMULATION AND LIPID MALABSORPTION
D. Noto 1 , A.B. Cefalu 1 , M. Mina 1 , A. Carroccio 1 , C.M. Barbagallo 1 , T. Montalcini 2 , L. Di Prima 1 , F. Fayer 1 , A. Pujia 2 , A. Notarbartolo 1 , M.R. Averna 1 . 1 Department of Clinical Medicine and Emerging Diseases, University of Palermo, Palermo, Italy; 2 Department of Internal Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy
Conclusions: The compound missense mutation G188E and D250N in the LPL gene was the genetic basis for the lack of post-heparin plasma LPL activity and hyperchylomicronemia described in this report. In children with severe hyperltriglyceridemia, after excluding all causes that can lead a child to epididymitis, such as urinary infection, malformations of the urinary tract and trauma, the hyperchylomicronemia should be considered the etiology of recurrent scrotal pain and/or acute epididymitis. Support: FAPESP/FAEPEX. PO3-80
LIPOPROTEIN(A) AND APOLIPOPROTEIN(A) POLYMORPHISM IN DIABETIC CHILDREN
K. Tosheska, D. Labudovic, S. Alabakovska, B. Todorova. Department of Medical and Experimental Biochemistry, Medical Faculty, Skopje, Macedonia It has been proved that atheromatous changes in vessels already appear in young children and adolescences. High plasma Lipoprotein(a)[Lp(a)] levels as well as low molecular weight (LMW) apolipoprotein(a)[apo(a)] isoforms are tought to be an independent risk factor for atherosclerosis and thrombosis. Thirty children with type 1 diabetes mellitus without microalbuminuria, aged 9 to 17 years, and 100 healthy children as controls were included in the study. Clinical history, physical examination, glycosilated hemoglobin (HbA1C), lipid profile including total cholesterol, HDL-C, LDL -C, triglycerides, ApoA1, ApoB, Lp(a) and apo(a) isoforms were determined. ApoA1, ApoB and Lp(a) were determined by use of nephelometric method. Apo(a) isoforms were separated by 3-15% gradient SDS-PAGE. Lp(a) levels were higher in diabetic subjects (15.19 ± 11.28 mg/dL) compared to control group (11.95 ± 5.98 mg/dL, p<0.05). HbA1C concentration in diabetic children was 7.49 ± 4.8% vs. 4.06 ± 0.38% in non-diabetic children. There was no difference in apo(a) isoform distribution between two groups. The most frequent isoforms were S4 from single banded and S4S3 from double banded in both study groups. Higher apo(a) molecular weight isoforms were associated with decreased Lp(a) concentrations in both diabetic and non-diabetic subjects. Levels of Lp(a) and apo(a) isoforms may be predictive of future cardiovascular disease in predisposed children. PO3-81
PARABOLIC RELATION BETWEEN PLASMA TRIGLYCERIDES AND LDL-CHOLESTEROL IN FAMILIAL COMBINED HYPERLIPIDEMIA: THE MULTIPLE-TYPE HYPERLIPIDEMIA EXPLAINED?
1 Clinical
M. Brouwers 1 , M. van Greevenbroek 1 , J. de Graaf 2 , A. Georgieva 1 , C. van der Kallen 1 , E. ter Avest 2 , C. Stehouwer 1 , A. Stalenhoef 2 , T. de Bruin 1,3 . 1 Department of Medicine, Academic Hospital Maastricht, Laboratory of Molecular Medicine and Endocrinology, and Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands; 2 Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; 3 Translational Medicine and Genetics, GlaxoSmithKline, NC, USA
Background and Aims: Type I hyperlipoproteinemia is a rare autossomic recessive disease characterized by a lack or absence of lipoprotein lipase (LPL) enzymatic activity caused by mutations in the LPL or apoCII (its cofactor) genes. Since LPL is a key protein in the catabolism of triglyceride-rich lipoproteins, patients with this deficiency develop severe hypertriglyceridemia that can lead to acute pancreatitis, eruptive xantomata and lipemia retinalis, the first presentation frequently being non-diagnosed. Methods: We describe here a 7 year old boy with type I hyperlipoproteinemia diagnosed at age of 5 months. Results: Undetectable post-heparin plasma LPL activity (radiometric method), recurrent episodes of scrotal pain and acute epididymitis (ultrasonography with Doppler imaging of the epididymis) as well as recurrent episodes of abdominal pain and episodes of acute pancreatitis (ultrasonography) were found. A compound heterozygosity for a G188E and D250N mutations in the LPL gene was detected by PCR-based sequencing methods.
Background and Aims: Triglyceride-rich VLDL1 and triglyceride-poorer VLDL2-particles are catabolized into small-dense and buoyant LDLparticles, respectively. This led us to hypothesize that plasma triglycerides and LDL-cholesterol levels are related parabolically, i.e. an increase in triglycerides in the lower range, i.e. 0.5-1.5 mmol/L, is associated with an increase in LDL-cholesterol, whereas a further increase in triglycerides is associated with a decrease in LDL-cholesterol in familial combined hyperlipidemia (FCHL). Methods: FCHL patients and their relatives (n=431) derived from the well-defined Nijmegen and Maastricht FCHL cohorts underwent lipid measurements twice, with a five-years interval. Three groups were defined: one with triglycerides <1.5 mmol/L at both time-points (group A), one group with triglycerides <1.5 mmol/L at one and >1.5 mmol/L at the other measurement (group B), and one group with triglycerides >1.5 mmol/L at both measurements (group C). Results: In a mixed linear model for repeated measurements, a positive relation between triglycerides and LDL-cholesterol was observed for males in group A (β=1.1, p<0.001), a negative relation in group C (β= -0.3, p=0.002), and a relation intermediate to group A and group C in group B (β=0.2, p=0.1) (figure). Such a parabolic relation was not observed in the female group.
PO3-79
UNIQUE CLINICAL PHENOTYPE IN A YOUNG BOY WITH TYPE I HYPERLIPOPROTEINEMIA ASSOCIATED WITH A COMBINED MUTATION ON THE LIPOPROTEIN LIPASE GENE
T.R. Takata 1,2,3 , R. Schreiber 1 , G. Guerra Jr 2 , I. Bendit 4 , E.C. de Faria 1,3 . Pathology Department, FCM, University of Campinas, Campinas, Sao Paulo, Brazil; 2 Pediatrics/CIPED Department, FCM, University of Campinas, Campinas, Sao Paulo, Brazil; 3 Dislipidemia Out-Patient Service, HC, University of Campinas, Sao Paulo, Campinas, Sao Paulo, Brazil; 4 Tumoral Biology Laboratory, Fundacao Pro-Sangue Hemocentro de Sao Paulo, Campinas, Sao Paulo, Brazil
76th Congress of the European Atherosclerosis Society, June 10–13, 2007, Helsinki, Finland
POSTER SESSIONS
Backgorund and Aims: Familial Hypobetalipoproteinemia (FHBL) is characterized by inherited low plasma levels of apolipoprotein B (apoB)containing lipoproteins. Mutations of the apoB gene encoding for truncated variants of apoB100 are responsible for some cases of FHBL. Truncated apoBs cause fatty liver due to impairment of hepatic lipoprotein export. In this paper we investigated whether apoB truncations shorter than apoB48, and an apoB missense mutation able to interfere with the action microsomial triglyceride transfer protein, may cause fat accumulation in the gut and fat malabsorption. Methods: Two kindred harboring novel ApoB mutations encoding for truncated ApoB28.25 and ApoB 34.8, and one with the known apoB missense mutation, R463W were studied. The probands were compared with 6 healthy controls and 6 patients with active celiac disease (CD). An oral fat load test supplemented with retinyl palmitate (RP) was administered to all subjects; FHBL and CD subjects underwent also gastro-intestinal endoscopic biopsies. Results: The oral fat load showed that plasma triglyceride and post prandial RP AUCs of FHBL probands were significantly reduced compared to controls and were similar to those of CD patients. Intestinal biopsies of FHBL patients in fasting status showed lipid droplets accumulating in the duodenal mucosa. Two FHBL probands were affected by type II diabetes mellitus and by metabolic syndrome. No post prandial overload of free fatty acids occurred; therefore this could not be the causal mechanism for the impaired glucose metabolism. Conclusion: FHBL due to heterozygous apoB mutations should be considered among the genetic causes of lipid malabsorption.
37
FAMILIAL HYPOBETALIPOPROTEINEMIA DUE TO APOLIPOPROTEIN B GENE MUTATIONS CAUSES INTESTINAL FAT ACCUMULATION AND LIPID MALABSORPTION
D. Noto 1 , A.B. Cefalu 1 , M. Mina 1 , A. Carroccio 1 , C.M. Barbagallo 1 , T. Montalcini 2 , L. Di Prima 1 , F. Fayer 1 , A. Pujia 2 , A. Notarbartolo 1 , M.R. Averna 1 . 1 Department of Clinical Medicine and Emerging Diseases, University of Palermo, Palermo, Italy; 2 Department of Internal Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy
Conclusions: The compound missense mutation G188E and D250N in the LPL gene was the genetic basis for the lack of post-heparin plasma LPL activity and hyperchylomicronemia described in this report. In children with severe hyperltriglyceridemia, after excluding all causes that can lead a child to epididymitis, such as urinary infection, malformations of the urinary tract and trauma, the hyperchylomicronemia should be considered the etiology of recurrent scrotal pain and/or acute epididymitis. Support: FAPESP/FAEPEX. PO3-80
LIPOPROTEIN(A) AND APOLIPOPROTEIN(A) POLYMORPHISM IN DIABETIC CHILDREN
K. Tosheska, D. Labudovic, S. Alabakovska, B. Todorova. Department of Medical and Experimental Biochemistry, Medical Faculty, Skopje, Macedonia It has been proved that atheromatous changes in vessels already appear in young children and adolescences. High plasma Lipoprotein(a)[Lp(a)] levels as well as low molecular weight (LMW) apolipoprotein(a)[apo(a)] isoforms are tought to be an independent risk factor for atherosclerosis and thrombosis. Thirty children with type 1 diabetes mellitus without microalbuminuria, aged 9 to 17 years, and 100 healthy children as controls were included in the study. Clinical history, physical examination, glycosilated hemoglobin (HbA1C), lipid profile including total cholesterol, HDL-C, LDL -C, triglycerides, ApoA1, ApoB, Lp(a) and apo(a) isoforms were determined. ApoA1, ApoB and Lp(a) were determined by use of nephelometric method. Apo(a) isoforms were separated by 3-15% gradient SDS-PAGE. Lp(a) levels were higher in diabetic subjects (15.19 ± 11.28 mg/dL) compared to control group (11.95 ± 5.98 mg/dL, p<0.05). HbA1C concentration in diabetic children was 7.49 ± 4.8% vs. 4.06 ± 0.38% in non-diabetic children. There was no difference in apo(a) isoform distribution between two groups. The most frequent isoforms were S4 from single banded and S4S3 from double banded in both study groups. Higher apo(a) molecular weight isoforms were associated with decreased Lp(a) concentrations in both diabetic and non-diabetic subjects. Levels of Lp(a) and apo(a) isoforms may be predictive of future cardiovascular disease in predisposed children. PO3-81
PARABOLIC RELATION BETWEEN PLASMA TRIGLYCERIDES AND LDL-CHOLESTEROL IN FAMILIAL COMBINED HYPERLIPIDEMIA: THE MULTIPLE-TYPE HYPERLIPIDEMIA EXPLAINED?
1 Clinical
M. Brouwers 1 , M. van Greevenbroek 1 , J. de Graaf 2 , A. Georgieva 1 , C. van der Kallen 1 , E. ter Avest 2 , C. Stehouwer 1 , A. Stalenhoef 2 , T. de Bruin 1,3 . 1 Department of Medicine, Academic Hospital Maastricht, Laboratory of Molecular Medicine and Endocrinology, and Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands; 2 Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; 3 Translational Medicine and Genetics, GlaxoSmithKline, NC, USA
Background and Aims: Type I hyperlipoproteinemia is a rare autossomic recessive disease characterized by a lack or absence of lipoprotein lipase (LPL) enzymatic activity caused by mutations in the LPL or apoCII (its cofactor) genes. Since LPL is a key protein in the catabolism of triglyceride-rich lipoproteins, patients with this deficiency develop severe hypertriglyceridemia that can lead to acute pancreatitis, eruptive xantomata and lipemia retinalis, the first presentation frequently being non-diagnosed. Methods: We describe here a 7 year old boy with type I hyperlipoproteinemia diagnosed at age of 5 months. Results: Undetectable post-heparin plasma LPL activity (radiometric method), recurrent episodes of scrotal pain and acute epididymitis (ultrasonography with Doppler imaging of the epididymis) as well as recurrent episodes of abdominal pain and episodes of acute pancreatitis (ultrasonography) were found. A compound heterozygosity for a G188E and D250N mutations in the LPL gene was detected by PCR-based sequencing methods.
Background and Aims: Triglyceride-rich VLDL1 and triglyceride-poorer VLDL2-particles are catabolized into small-dense and buoyant LDLparticles, respectively. This led us to hypothesize that plasma triglycerides and LDL-cholesterol levels are related parabolically, i.e. an increase in triglycerides in the lower range, i.e. 0.5-1.5 mmol/L, is associated with an increase in LDL-cholesterol, whereas a further increase in triglycerides is associated with a decrease in LDL-cholesterol in familial combined hyperlipidemia (FCHL). Methods: FCHL patients and their relatives (n=431) derived from the well-defined Nijmegen and Maastricht FCHL cohorts underwent lipid measurements twice, with a five-years interval. Three groups were defined: one with triglycerides <1.5 mmol/L at both time-points (group A), one group with triglycerides <1.5 mmol/L at one and >1.5 mmol/L at the other measurement (group B), and one group with triglycerides >1.5 mmol/L at both measurements (group C). Results: In a mixed linear model for repeated measurements, a positive relation between triglycerides and LDL-cholesterol was observed for males in group A (β=1.1, p<0.001), a negative relation in group C (β= -0.3, p=0.002), and a relation intermediate to group A and group C in group B (β=0.2, p=0.1) (figure). Such a parabolic relation was not observed in the female group.
PO3-79
UNIQUE CLINICAL PHENOTYPE IN A YOUNG BOY WITH TYPE I HYPERLIPOPROTEINEMIA ASSOCIATED WITH A COMBINED MUTATION ON THE LIPOPROTEIN LIPASE GENE
T.R. Takata 1,2,3 , R. Schreiber 1 , G. Guerra Jr 2 , I. Bendit 4 , E.C. de Faria 1,3 . Pathology Department, FCM, University of Campinas, Campinas, Sao Paulo, Brazil; 2 Pediatrics/CIPED Department, FCM, University of Campinas, Campinas, Sao Paulo, Brazil; 3 Dislipidemia Out-Patient Service, HC, University of Campinas, Sao Paulo, Campinas, Sao Paulo, Brazil; 4 Tumoral Biology Laboratory, Fundacao Pro-Sangue Hemocentro de Sao Paulo, Campinas, Sao Paulo, Brazil
76th Congress of the European Atherosclerosis Society, June 10–13, 2007, Helsinki, Finland
POSTER SESSIONS
Backgorund and Aims: Familial Hypobetalipoproteinemia (FHBL) is characterized by inherited low plasma levels of apolipoprotein B (apoB)containing lipoproteins. Mutations of the apoB gene encoding for truncated variants of apoB100 are responsible for some cases of FHBL. Truncated apoBs cause fatty liver due to impairment of hepatic lipoprotein export. In this paper we investigated whether apoB truncations shorter than apoB48, and an apoB missense mutation able to interfere with the action microsomial triglyceride transfer protein, may cause fat accumulation in the gut and fat malabsorption. Methods: Two kindred harboring novel ApoB mutations encoding for truncated ApoB28.25 and ApoB 34.8, and one with the known apoB missense mutation, R463W were studied. The probands were compared with 6 healthy controls and 6 patients with active celiac disease (CD). An oral fat load test supplemented with retinyl palmitate (RP) was administered to all subjects; FHBL and CD subjects underwent also gastro-intestinal endoscopic biopsies. Results: The oral fat load showed that plasma triglyceride and post prandial RP AUCs of FHBL probands were significantly reduced compared to controls and were similar to those of CD patients. Intestinal biopsies of FHBL patients in fasting status showed lipid droplets accumulating in the duodenal mucosa. Two FHBL probands were affected by type II diabetes mellitus and by metabolic syndrome. No post prandial overload of free fatty acids occurred; therefore this could not be the causal mechanism for the impaired glucose metabolism. Conclusion: FHBL due to heterozygous apoB mutations should be considered among the genetic causes of lipid malabsorption.
37