Comparison of anthropometric measurements in children to predict metabolic syndrome in adolescence: analysis of prospective cohort data.

OBJECTIVES: The optimal screening measures for obesity in children remain controversial. Our study aimed to determine the anthropometric measurement at age 10 years that most strongly predicts the incidence of cardio-metabolic risk factors at age 13 years. SUBJECTS/METHODS: This was a prospective cohort study of a population-based cohort of 438 children followed between age 7 and 13 years of age. The main exposure variables were adiposity at age 10 years determined from body mass index (BMI) Z-score, waist circumference (WC) Z-score, waist-to-hip ratio and waist-to-height ratio. Outcome measures included systolic (SBP) and diastolic blood pressure (DBP), fasting high-density (HDL-c) and low-density lipoprotein cholesterol (LDL-c), triglycerides, insulin and glucose (homeostasis model of assessment, HOMA), and the presence of metabolic syndrome (MetS). RESULTS: WC Z-score at age 10 years was a stronger predictor of SBP (ß 0.21, R(2) 0.38, P<0.001 vs ß 0.30, R(2) 0.20, P<0.001) and HOMA (ß 0.51, R(2) 0.25, P<0.001 vs 0.40, R(2) 0.19, P<0.001) at age 13 years compared with BMI Z-score. WC relative to height and hip was stronger predictors of cardio- metabolic risk than BMI Z-score or WC Z-score. The relative risk (RR) of incident MetS was greater for an elevated BMI Z-score than for an elevated WC (girls: RR 2.52, 95% confidence interval (CI): 1.46-4.34 vs RR 1.56, 95% CI 1.18-2.07) and (boys: RR 2.86, 95% CI 1.79-4.62 vs RR 2.09, 95% CI 1.59-2.77). CONCLUSIONS: WC was a better predictor of SBP and HOMA compared with BMI or WC expressed relative to height or hip circumference. BMI was associated with higher odds of MetS compared with WC. Thus, BMI and WC may each be clinically relevant markers of different cardio-metabolic risk factors, and important in informing obesity-related prevention and treatment strategies.

Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX.

Hyaluronan (HA), a large glycosaminoglycan abundant in the extracellular matrix, is important in cell migration during embryonic development, cellular proliferation, and differentiation and has a structural role in connective tissues. The turnover of HA requires endoglycosidic breakdown by lysosomal hyaluronidase, and a congenital deficiency of hyaluronidase has been thought to be incompatible with life. However, a patient with a deficiency of serum hyaluronidase, now designated as mucopolysaccharidosis IX, was recently described. This patient had a surprisingly mild clinical phenotype, including notable periarticular soft tissue masses, mild short stature, an absence of neurological or visceral involvement, and histological and ultrastructural evidence of a lysosomal storage disease. To determine the molecular basis of mucopolysaccharidosis IX, we analyzed two candidate genes tandemly distributed on human chromosome 3p21.3 and encoding proteins with homology to a sperm protein with hyaluronidase activity. These genes, HYAL1 and HYAL2, encode two distinct lysosomal hyaluronidases with different substrate specificities. We identified two mutations in the HYAL1 alleles of the patient, a 1412G --> A mutation that introduces a nonconservative amino acid substitution (Glu268Lys) in a putative active site residue and a complex intragenic rearrangement, 1361del37ins14, that results in a premature termination codon. We further show that these two hyaluronidase genes, as well as a third recently discovered adjacent hyaluronidase gene, HYAL3, have markedly different tissue expression patterns, consistent with differing roles in HA metabolism. These data provide an explanation for the unexpectedly mild phenotype in mucopolysaccharidosis IX and predict the existence of other hyaluronidase deficiency disorders.