Homozygous nonsense and frameshift mutations of the ACTH receptor in children with familial glucocorticoid deficiency (FGD) are not associated with long-term mineralocorticoid deficiency
| Autor: | Li F. Chan, Stephen M. P. O'Riordan, Heiko Krude, Colm Costigan, Martin O. Savage, Adrian J. L. Clark, Paolo Cavarzere, Colin Ball, Louise A. Metherell, Sally Ann Lynch |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty endocrine system Adolescent medicine.drug_class Endocrinology Diabetes and Metabolism Fludrocortisone Nonsense mutation Adrenal Gland Diseases 030209 endocrinology & metabolism Biology Frameshift mutation 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine Mineralocorticoids medicine Humans ACTH receptor Adrenal Child Frameshift Mutation Glucocorticoids 030304 developmental biology Retrospective Studies 0303 health sciences Infant Newborn Infant Original Articles Mineralocorticoid secretion 3. Good health Pedigree Receptors Corticotropin Mineralocorticoid Codon Nonsense Child Preschool Female Isolated Glucocorticoid Deficiency hormones hormone substitutes and hormone antagonists Glucocorticoid medicine.drug |
| Zdroj: | Clinical Endocrinology |
| ISSN: | 1365-2265 0300-0664 |
| Popis: | Summary Objective Familial glucocorticoid deficiency (FGD) is a rare auto- somal recessive disease characterized by isolated glucocorticoid deficiency with preserved mineralocorticoid secretion. Mutations in the ACTH receptor (MC2R) account for approximately 25% of all FGD cases, but since these are usually missense mutations, a degree of receptor function is frequently retained. A recent report, however, suggested that disturbances in the renin-aldosterone axis were seen in some patients with potentially more severe MC2R mutations. Furthermore, MC2R knock out mice have overt aldosterone deficiency and hyperkalaemia despite preservation of a normal zona glomerulosa. We wished to determine whether a group of patients with severe nonsense mutations of the MC2R exhibited evidence of mineralocorticoid deficiency, thereby challenging the conventional diagnostic feature of FGD which might result in diagnostic misclassification. Design Clinical review of patients with nonsense MC2R mutations. Patients Between 1993 and 2008, 164 patients with FGD were screened for mutations in the MC2R. Totally 42 patients (34 families) were found to have mutations in the MC2R. Of these, 6 patients (4 families) were found to have homozygous nonsense or frameshift mutations. Results Mild disturbances in the renin-angiotensin-aldosterone axis were noted in four out of six patients, ranging from slightly elevated plasma renin levels to low aldosterone levels, although frank mineralocorticoid deficiency or electrolyte disturbance were not found. No patient required fludrocortisone replacement. Conclusion Severe nonsense and frameshift MC2R mutations are not associated with clinically significant mineralocorticoid deficiency and are thus unlikely to require long-term mineralocorticoid replacement. |
| Databáze: | OpenAIRE |
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