Effectiveness of current interventions in obese New Zealand children and adolescents.

AIMS: To determine the effectiveness of current interventions in New Zealand in obese children and adolescents accessing either a standard model of care (medical input alone or with the addition of dietitian and physical activity input), or one of the country's long-standing multi-disciplinary intervention programmes. METHODS: Data were recorded over approximately 2.1 years of intervention from 290 patients across four centres in New Zealand, who manage obese and overweight children and adolescents aged 3-16 years in paediatric clinics. RESULTS: There was a small but significant annual reduction in BMI SDS irrespective of the nature of intervention (-0.15 overall). There was no significant difference in BMI SDS between interventions. The extent of BMI SDS reduction decreased with increasing age at first outpatient attendance (p=0.0006). BMI SDS reduction was unaffected by ethnicity or gender. CONCLUSIONS: Mild reductions in BMI SDS are achievable in children being referred to and managed for obesity by a range of models. It is important that paediatricians are proactive in identifying and addressing obesity with families. Further research is required to evaluate multi-disciplinary intervention programmes, and how their effectiveness can be increased, given their recognised benefits in improving cardiovascular and metabolic profile, as well as BMI SDS.

Skeletal phenotype of mandibuloacral dysplasia associated with mutations in ZMPSTE24.

Mandibuloacral dysplasia (MAD) is a rare recessively inherited premature aging disease characterized by skeletal and metabolic anomalies. It is part of the spectrum of diseases called laminopathies and results from mutations in genes regulating the synthesis of the nuclear laminar protein, lamin A. Homozygous or compound heterozygous mutations in the LMNA gene, which encodes both the precursor protein prelamin A and lamin C, are the commonest cause of MAD type A. In a few cases of MAD type B, mutations have been identified in the ZMPSTE24 gene encoding a zinc metalloproteinase important in the post-translational modification of lamin A. Here we describe a new case of MAD resulting from compound heterozygote mutations in ZMPSTE24 (p.N256S/p.Y70fs). The patient had typical skeletal changes of MAD, but in addition a number of unusual skeletal features including neonatal tooth eruption, amorphous calcific deposits, submetaphyseal erosions, vertebral beaking, severe cortical osteoporosis and delayed fracture healing. Treatment with conventional doses of pamidronate improved estimated volumetric bone density in the spine but did not arrest cortical bone loss. We reviewed the literature on cases of MAD associated with proven LMNA and ZMPSTE24 mutations and found that the unusual features described above were all substantially more prevalent in patients with mutations in ZMPSTE24 than in those with LMNA mutations. We conclude that MAD associated with ZMPSTE24 mutations has a more severe phenotype than that associated with LMNA mutations--probably reflecting the greater retention of unprocessed farnesylated prelamin A in the nucleus, which is toxic to cells.