Mutations in MC4R result in a distinct obesity syndrome that is inherited in a codominant manner. Mutations leading to complete loss of function are associated with a more severe phenotype. The correlation between the signaling properties of these mutant receptors and energy intake emphasizes the key role of this receptor in the control of eating behavior in humans.

No abstract

For the full versions of these articles see bmj.comRickets in children and osteomalacia in adults are the classic manifestations of profound vitamin D deficiency. In recent years, however, non-musculoskeletal conditions-including cancer, metabolic syndrome, infectious and autoimmune disorders-have also been found to be associated with low vitamin D levels. 1 The spectrum of these common disorders is of particular concern because observational studies have demonstrated that vitamin D insufficiency is widespread in many northern regions of the world, including industrialised countries. 2 3 The increasing prevalence of disorders linked to vitamin D deficiency is reflected in the several hundred children with rickets treated each year in the UK. 4 However, these children represent a small proportion of the individuals with a suboptimal vitamin D status in the UK population. 1 3 5 A recent nationwide survey in the United Kingdom showed that more than 50% of the adult population have insufficient levels of vitamin D and that 16% have severe deficiency during winter and spring. 5 The survey also demonstrated a gradient of prevalence across the UK, with highest rates in Scotland, northern England, and Northern Ireland. 5 People with pigmented skin are at high risk, as are the elderly; obese individuals; those with malabsorption, short bowel, or renal or liver disease; and individuals t aking anticonvulsants, rifampicin, or highly active anti retroviral drugs.In this article we discuss the diagnosis and management of vitamin D insufficiency and deficiency in children and adults according to evidence from descriptive and observational studies, randomised trials, and metaanalyses. what are the sources of vitamin D?Vitamin D refers to the precursors of the active secosteroid hormone 1,25-dihydroxyvitamin D 3 (1,25-OH 2 D 3 ), also known as calcitriol. The major natural source of vitamin D is from skin photosynthesis following ultraviolet B solar irradiation (box 1).In a fair skinned person, 20 minutes to 30 minutes of sunlight exposure on the face and forearms at midday is estimated to generate the equivalent of around 2000 IU of vitamin D. Two or three such sunlight exposures a week are sufficient to achieve healthy vitamin D levels in summer Vitamin D insufficiency is common in the UK population Vitamin D deficiency typically presents with bony deformity (rickets) or hypocalcaemia in infancy and childhood, and with musculoskeletal pain and weakness in adults Many other health problems-including cardiovascular disease, type 2 diabetes, several cancers, and autoimmune conditions-have recently been associated with vitamin D insufficiency Risk factors include skin pigmentation, use of sunscreen or concealing clothing, being elderly or institutionalised, obesity, malabsorption, renal and liver disease, and anticonvulsant use Vitamin D status is most reliably determined by assay of serum 25-hydroxyvitamin D (25-OHD) Rickets and osteomalacia should be treated with high strength calciferol (ergocalciferol or colecalciferol) for 8-...