Intermediate-Term Efficacy and Tolerance of Statins in Children.

OBJECTIVES: To evaluate the intermediate-term efficacy and tolerance of statins in children and adolescents with familial hypercholesterolemia. STUDY DESIGN: A total of 131 children or adolescents treated with statins for familial hypercholesterolemia were prospectively included. The efficacy of treatment was established by the percentage of children who achieved low density lipoprotein-cholesterol (LDL-C) levels <160 mg/dL during treatment. Treatment tolerance was evaluated by the occurrence of clinical or laboratory side effects, regularity of increases in height and weight, and pubertal development. RESULTS: The median duration of treatment with statins was 4 years. A median decrease of 32% in LDL-C levels was observed (P < .0001). The therapeutic target (LDL-C <160 mg/dL) was achieved in 67% of cases. Increases in height and weight and sexual maturation were not affected by the treatment. Minor side effects were reported for 24 (18.4%) patients including 3 cases of a clinically asymptomatic increase in creatine phosphokinase (CPK) levels, 2 cases of an increase in CPK levels with muscular symptoms, 14 cases of myalgia without an increase in CPK levels, 3 cases of abdominal pain, 1 case of dysuria, and 1 case of diffuse pain. None of these side effects led to the discontinuation of statin therapy, although a change of statin was required in 7 cases. This new statin was tolerated in all cases. No patients had abnormal liver function during treatment. CONCLUSIONS: The results of this large cohort confirm the intermediate-term safety and efficacy of statin therapy in children with familial hypercholesterolemia.

Association of arterial stiffness and endothelial dysfunction with metabolic syndrome in obese children.

OBJECTIVE: We investigated whether metabolic syndrome, defined in 3 different ways (2 commonly used and 1 novel) is associated with arterial alterations in obese children. STUDY DESIGN: The study group comprised 384 obese children age 2.5 to 18 years. Blood pressure, fasting blood glucose, blood insulin, plasma lipids, and body composition were measured. Noninvasive ultrasound measurements were obtained in 161 patients to investigate arterial mechanical properties and endothelial function. RESULTS: The prevalence of metabolic syndrome was 10.4%. Intima-media thickness correlated positively with low-density lipoprotein cholesterol (r = .21; P < .01) and negatively with high-density lipoprotein cholesterol (r = -.17; P < .05). In adolescents (11 to 18 years), cross-sectional vascular compliance correlated negatively with abdominal fat (r = -.22; P = .02). The only synergistic effects among individual metabolic syndrome components was an effect of insulinemia and systolic blood pressure on cross-sectional compliance (4.05; P < .05). No significant difference in vascular variables was found between the patients with and without metabolic syndrome using any of the 3 definitions. CONCLUSION: Metabolic syndrome in obese children is not related to arterial variables, whereas several of its individual components are associated with vascular alterations. These data suggest that the value of the metabolic syndrome as a predictor of future cardiovascular events in children remains to be prospectively evaluated. In the meantime, individual cardiovascular risk factors should be evaluated and controlled.

Homozygous null mutation of the melanocortin-4 receptor and severe early-onset obesity.

OBJECTIVE: To describe the clinical and biological phenotype of a child who is severely obese and is homozygous for a new melanocortin-4 receptor (MC4R) gene mutation leading to a truncated receptor. STUDY DESIGN: Direct sequencing of the MC4R gene was performed in a child who was severely obese and his relatives. Phenotypic characterization included weight evolution, anthropometric parameters, and endocrine and metabolic complications. Growth curves were compared with those of children carrying leptin receptor (LEPR) homozygous mutation, MC4R heterozygous mutations, and MC4R wild type allele. RESULTS: We found a homozygous 2-base pair deletion (del 346-347AG) leading to a stop codon. This new mutation leads to a truncated MC4R after the second transmembrane domain in a 3-year-old boy with severe early-onset obesity. Segregation analysis of the mutation showed that the 2 parents and 2 adult relatives were heterozygous carriers for the mutation. Heterozygous carriers displayed an obese phenotype, but with a variable degree of severity. The homozygous carrier of the mutation was hyperphagic and showed a rapid increase in weight in the very first months of life. His weight evolution closely resembled that of patients who are LEPR deficient, but markedly differed with that of children carrying either heterozygous MC4R mutations or MC4R wild type allele. No other hormonal or metabolic anomaly was found in the child. CONCLUSIONS: This phenotype of a boy carrying a new homozygous MC4R mutation confirms the critical role of MC4R in the early dynamic of weight gain and phenotypic differences with heterozygous carriers.