Register for New cases of obesity due to proopiomelanocortin deficiency reported
Obesity Genomics and GeneticsDecember 15, 2003
Scientists report three new cases of obesity due to proopiomelanocortin deficiency and the results of treatment with thyroid hormone and ACTH4-10.
According to recent research from an international team of researchers, "The symptoms of severe early-onset obesity, adrenal insufficiency, and red hair define the proopiomelanocortin (POMC) deficiency syndrome as described so far in two children with complete loss-of-function mutations of the human POMC gene. In POMC deficiency, obesity reflects the lack of POMC-derived peptides as ligands at the melanocortin (MC) MC4 and MC3 receptors, which are expressed in the hypothalamic leptin-melanocortin pathway of body weight regulation."
"Hypocortisolism and alteration of pigmentation are caused by the lack of POMC-derived peptides at the adrenal MC2 receptor and the skin MC1 receptor, respectively," said Heiko Krude at Humboldt-University Berlin in Germany and collaborators in Germany, the Netherlands, Slovenia, and Switzerland. "Here we describe three new cases of complete loss-of-function mutations of the POMC gene. Patients were diagnosed based on the clinical trials of red hair, adrenal insufficiency, and early-onset severe obesity. One previously described translation initiation mutation (C3804A) as well as one new nonsense (A6851T) and two new frame-shift mutations (6996del and 7100 + 2G) were found in homozygosity or compound heterozygosity."
"The heterozygous parents were found to have high normal or mildly elevated body weight, suggesting a dosage effect of the POMC gene product on weight regulation," reported the researchers. "To compensate for the lack of hypothalamic melanocortin function, we initiated a trial in the two previously published patients with intranasal ACTH4-10, a melanocortin fragment for which an anorexic effect has been described recently. During three months with increasing doses of ACTH4-10, no change of body weight or metabolic rate was observed, suggesting that at least in these two POMC-deficient patients ACTH4-10 is without any compensatory effect."
"In the same two patients, further investigation revealed a mildly elevated TSH," stated Krude and associates. "However, a one-year treatment with thyroid hormone did not result in a significant reduction of body weight."
Krude and colleagues published their study in the Journal of Clinical Endocrinology and Metabolism (Obesity due to proopiomelanocortin deficiency: Three new cases and treatment trials with thyroid hormone and ACTH4-10. J Clin Endocrinol Metab, 2003;88(10):4633-4640).
For additional information, contact Heiko Krude, Institute of Pediatric Endocrinology, University Children's Hospital, Charite, Humboldt-University Berlin, D-13353 Berlin, Germany. E-mail: heiko.krude@charite.de.
Publisher contact information for the Journal of Clinical Endocrinology and Metabolism is: Endocrine Society, 4350 East West Highway Suite 500, Bethesda, MD 20814-4110, USA.
The information in this article comes under the major subject areas of Obesity Genomics and Genetics, Genetic Disorder, Endocrinology, Hormonal, Mutation, and Proteomics. This article was prepared by Health & Medicine Week editors from staff and other reports.
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