LDL-C is one of the strongest markers for atherosclerosis and therapeutic decisions in children are based on its levels. Friedewald formula (FF) which is usually used for the calculation of LDL-C ...(cLDL-C); and Anandaraja's formula (AF) may under- or overestimate actual levels.
To compare cLDL-C with directly measured LDL-C (dLDL-C) as a screening tool and to evaluate dyslipidemic children.
The study population consisted of 1005 children, 2–18years, 688 of whom underwent lipid screening in a regular check-up (group A); and 317 were dyslipidemic (LDL-C ≥130mg/dl) (group B). A fasting serum lipid profile was assessed. LDL-C was measured using a homogenous assay and was calculated using FF and AF.
Each method of calculating LDL-C was highly correlated to dLDL-C. Using FF, cLDL-C was lower than dLDL-C in 75.6% (group A) and in 77.3% (group B) of children; the mean difference was significant in dyslipidemic group. Moreover, in group B, 25% of children with boundary high and 12% with high dLDL-C would be misclassified. Using AF, LDL-C was higher than dLDL-C; the mean difference was significant in group A. Based on cLDL-C, 52% of group A with borderline dLDL-C and 27.5% of group B children with boundary high dLDL-C would be considered as dyslipidemic and eligible for medication respectively.
Comparing two methods of calculated LDL-C with directly measured LDL-C. FF was more accurate as a screening tool while AF was more accurate in the evaluation and follow-up of the dyslipidemic group.
Childhood/Adult-onset Lysosomal Acid Lipase Deficiency (LAL-D) is a recessive disorder due to loss of function variants of LAL, the enzyme which hydrolyses cholesteryl esters, derived from ...internalized apoB containing lipoproteins. The disease is characterized by multi-organ involvement including the liver, spleen, intestine and cardiovascular system.
The aim of this study was the clinical and molecular characterization of 14 (13 unrelated) previously unreported patients with childhood-onset LAL-D.
Data collected included clinical and laboratory investigations, liver imaging, liver biopsy and LIPA gene analysis. The response to lipid-lowering medications, liver transplantation and enzyme replacement therapy (ERT) was reported for some patients.
LAL-D was suspected at 4.4 ± 3.3 years of age for the presence of hepatomegaly, elevated serum transaminases and hypercholesterolemia, and was confirmed by liver biopsy/imaging and LAL assay. The follow up period ranged from 3 to 40 years (mean 7.8 ± 4.0 years in 13 cases). Patients treated with statins with or without ezetimibe showed 28% reduction of plasma LDL-cholesterol without a tangible effect on liver enzymes; some patients receiving ERT showed normalized lipoprotein profile and transaminase levels.
The common c.894G > A variant was observed in homozygosity or compound heterozygosity in 10 patients. We found seven previously reported variants: p.(Trp140*), p.(Arg218*), p.(Gly266*), p.(Thr288Ile), p.(Leu294Ser), p.(His295Tyr) and p.(Gly342Arg) and two novel variants: p.(Asp345Asn), affecting the LAL catalytic triad, and c.229+3A > C, affecting splicing. Homozygosity for p.(Thr288Ile) or c.229+3A > C was associated with a severe phenotype.
This study provides additional data on the features of childhood-onset LAL-D and describes two novel pathogenic variants of the LIPA gene.
•Clinical and genetic study of 14 patients with childhood-onset LAL-D.•Four patients were homozygous for the common c.894G > A variant of LIPA gene.•In six patients c.894G > A was associated with other pathogenic variants.•A novel missense and a novel splicing pathogenic variant were identified.•The putative geographical origin of three variants is suggested.
The purpose of this study was to investigate, by a prospective, self-controlled method, whether early treatment with carbamazepine monotherapy can alter bone metabolism in ambulatory epileptic ...children with adequate sun exposure, based on the determination of total serum alkaline phosphatase and its bone isoenzyme activities. Serum total alkaline phosphatase and its bone, liver, and intestinal isoenzyme activities were evaluated in 22 epileptic ambulatory children (13 males and 9 females, aged from 5 to 12 years) before and at 3, 6, and 12 months of carbamazepine monotherapy. Serum concentrations of other biochemical markers of bone and liver metabolism, such as calcium, phosphorus, magnesium, γ-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, were also measured in the study participants before and at 6 and 12 months of treatment. Carbamazepine was prescribed at normal dosages (16.4-20 mg/kg/day). Serum total alkaline phosphatase activities were significantly increased at 3 (P = .000), 6 (P = .024), and 12 (P = .037) months of treatment; serum bone alkaline phosphatase activities at 3 (P = .000), 6 (P = .008), and 12 (P = .017) months of treatment; and serum liver alkaline phosphatase activities at 3 (P = .000), 6 (P = .049), and 12 (P = .008) months of treatment, whereas serum intestinal alkaline phosphatase isoenzyme activity was significantly increased only at 3 months of treatment (P = .035). Serum γ-glutamyltransferase activities were also significantly increased at 6 (P = .000) and 12 (P = .000) months of treatment. No significant changes in the concentrations of serum calcium, phosphorus, magnesium, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase were noted at 6 and 12 months of treatment. There was a significant correlation between serum γ-glutamyltransferase activities and serum total alkaline phosphatase activities (r = .689, P = .000 at 6 months; r = .493, P = .020 at 12 months), bone alkaline phosphatase activities (r = .700, P = .000 at 6 months; r = .466, P = .029 at 12 months), and liver alkaline phosphatase activities (r = .427, P = .047 at 6 months; r = .425, P = .048 at 12 months). These findings indicate that ambulatory children who receive carbamazepine monotherapy, even when residing in a country with adequate sunlight, can have their bone metabolism altered early in the course of treatment, as indicated by the elevated activities of serum bone alkaline phosphatase isoenzyme. This early alteration in bone metabolism is probably due to the hepatic enzyme-inducing character of carbamazepine. (J Child Neurol 2005;20:513-516).
Congenital cataracts-facial dysmorphism-neuropathy syndrome (CCFDN, MIM: 604168), is a recently delineated neurogenetic disease causing recurrent episodes of rhabdomyolysis; prevention and early ...diagnosis of rhabdomyolysis should be part of the clinical management of the disease.
The role of homozygosity for the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene as an independent risk factor for primary and recurrent stroke has been questioned, ...although recent data appear to be supportive. However, the association of homozygous C677T MTHFR mutation with silent brain infarctions in infancy has not been reported. The authors describe an 11-month-old male who had suffered a silent brain infarction followed by a symptomatic arterial stroke. The evaluation revealed mildly elevated homocysteine levels secondary to homozygous C677T alleles for MTHFR and iron deficiency anemia. An extensive evaluation for other causes of infarction was negative. We suggest that the mother’s homozygous MTHFR status played a role in the early onset of stroke and that iron deficiency anemia may have contributed to the recurrence. The patient was treated with anticoagulation therapy, folic acid, and iron supplementation and has not had a recurrent event during 3 years of follow-up. This case provides further evidence that homozygous MTHFR mutation is a predisposing factor for early and recurrent pediatric stroke, including silent infarcts, especially in the presence of other risk factors.
An informed parental consent was obtained, and the study was approved by the Institutional Review Board of “Attikon” University Hospital. Serum sodium, potassium, and magnesium in 32 children with ...epilepsy during levetiracetam monotherapy Parameters Pretreatment 2 months P 6 months P Sodium (mmol/L) 140 ± 2.72 (140) 140 ± 2.29 (141) 0.991 140 ± 2.24 (140.5) 0.345 Potassium (mmol/L) 4.59 ± 0.33 (4.55) 4.61 ± 0.37 (4.60) 0.922 4.67 ± 0.37 (4.60) 0.450 Magnesium (mg/dL) 2.17 ± 0.15 (2.15) 2.15 ± 0.18 (2.15) 0.314 2.13 ± 0.17 (2.10) 0.208 Values are expressed as mean ± SD, (median). There are limitations to this study: the number of patients studied was small and changes in serum/urine osmolality and urine electrolytes were not measured.
•This is an analysis from HELLAS-FH registry.•1655 adults with heterozygous FH (HeFH) were included.•Over half of HeFH adults have overweight or obesity.•Obesity was associated with increased ...prevalence of coronary artery disease.
Familial hypercholesterolemia (FH) and obesity are well-established risk factors of atherosclerotic cardiovascular disease (ASCVD). Despite high prevalence, their joint association with ASCVD remains largely unknown.
To investigate the association of obesity with prevalent ASCVD in individuals with heterozygous FH (HeFH) enrolled in the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH).
FH diagnosis was based on Dutch Lipid Clinic Network (DLCN) criteria. Adults with at least possible FH diagnosis (DLCN score ≥3) and available body mass index (BMI) values were included. Homozygous FH individuals were excluded.
1655 HeFH adults (mean age 51.0 ± 14.4 years, 48.6% female) were included; 378 (22.8%) and 430 (26.0%) were diagnosed with probable and definite FH, respectively. Furthermore, 371 participants (22.4%) had obesity and 761 (46.0%) were overweight. Prevalence of ASCVD risk factors increased progressively with BMI. Prevalence of coronary artery disease (CAD) was 23.4% (3.2% for stroke and 2.7% for peripheral artery disease PAD), and increased progressively across BMI groups. After adjusting for traditional ASCVD risk factors and lipid-lowering medication, individuals with obesity had higher odds of established CAD (OR: 1.54, 95% CI: 1.04–2.27, p = 0.036) as well as premature CAD (OR: 1.74, 95% CI: 1.17–2.60, p = 0.009) compared with those with normal BMI. No association was found with stroke or PAD.
Over half of adults with HeFH have overweight or obesity. Obesity was independently associated with increased prevalence of CAD in this population.
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Three physical signs, namely tendon xanthomas, corneal arcus and xanthelasma, have been associated with heterozygous familial hypercholesterolemia (heFH). The prevalence and clinical significance of ...these signs are not well established among contemporary heFH individuals. This study explored the frequency as well as the association of these physical signs with prevalent atherosclerotic cardiovascular disease (ASCVD) in heFH individuals.
Data from the Hellenic Familial Hypercholesterolemia Registry were applied for this analysis. The diagnosis of heFH was based on the Dutch Lipid Clinic Network Score. Multivariate logistic regression analysis was conducted to examine the association of heFH-related physical signs with prevalent ASCVD.
Adult patients ( n = 2156, mean age 50 ± 15 years, 47.7% women) were included in this analysis. Among them, 14.5% had at least one heFH-related physical sign present. The prevalence of corneal arcus before the age of 45 years was 6.6%, tendon xanthomas 5.3%, and xanthelasmas 5.8%. Among physical signs, only the presence of corneal arcus before the age of 45 years was independently associated with the presence of premature coronary artery disease (CAD). No association of any physical sign with total CAD, stroke or peripheral artery disease was found. Patients with physical signs were more likely to receive higher intensity statin therapy and dual lipid-lowering therapy, but only a minority reached optimal lipid targets.
The prevalence of physical signs is relatively low in contemporary heFH patients. The presence of corneal arcus before the age of 45 years is independently associated with premature CAD.
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