Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2003) 5 S21

Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK.


The heterogeneity of human morbid obesity is becoming increasingly apparent with a growing number of monogenic disorders leading to profound dysregulation of body fat mass being identified. Congenital leptin deficiency is associated with extreme hyperphagia and hypogonadotropic hypogonadism. Three subjects with this condition are currently undergoing therapeutic trial of recombinant human leptin with markedly beneficial effects on appetite and weight. Leptin treatment has permitted normal pubertal progression at the appropriate age in one subject and has not been associated with premature onset of puberty in two other patients. The finding of a subtle metabolic phenotype in heterozygotes for nonsense mutations in the leptin gene provides some evidence that leptin may exert more than a simple 'threshold' effect on development of very low plasma concentrations. A single individual with mutations in prohormone convertase 1 with morbid obesity has been reported and in the absence of murine models of PC1 deficiency, this patient provides important insights into the function of this enzyme. Congenital deficiency of POMC results in hypoadrenalism, red hair and obesity, and we have recently found a family with missense mutation in POMC which cosegregates with obesity in an autosomal dominant fashion. The mechanism of this is currently being explored. Mutations in the melanocortin 4 receptor represent by far the commonest form of monogenic obesity. Thus far we have found up to 5% of all severe obese children harbouring such a mutation. Children with MC4 mutations show striking acceleration of linear growth and markedly increased bone mass at an early age. The continuing dissection of heterogeneity of severe obesity should aid genetic counselling, prognostication and development of specific therapies.

Volume 5

22nd Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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