Six cases with severe insulin resistance (SIR) associated with mutations of insulin receptor: Is a Bartter-like syndrome a feature of congenital SIR?
| Autor: | Franco Cerutti, Franco Meschi, C. Monciotti, Ivana Rabbone, Valeria Favalli, Alfonso Galderisi, C. Colombo, Riccardo Bonfanti, Ornella Massa, Dario Iafusco, Fabrizio Barbetti, Enzo Bonora, Sara Gombos, Valeria Grasso |
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| Přispěvatelé: | Grasso, V, Colombo, C, Favalli, V, Galderisi, A, Rabbone, I, Gombos, S, Bonora, E, Massa, O, Meschi, F, Cerutti, F, Iafusco, Dario, Bonfanti, R, Monciotti, C, Barbetti, F. |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Pediatrics medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism Gene mutation Bartter syndrome Extreme insulin resistance Severity of Illness Index Endocrinology Internal medicine Bartter's syndrome Insulin receptor Mutation Acanthosis Nigricans Bartter Syndrome Child Preschool Donohue Syndrome Female Humans Infant Infant Newborn Insulin Resistance Nephrocalcinosis Receptor Insulin Internal Medicine medicine Insulin Child Preschool Acanthosis nigricans business.industry General Medicine medicine.disease Newborn Hyperaldosteronism Diabetes and Metabolism Bartter’s syndrome Donohue syndrome business Hyperinsulinism Receptor |
| Popis: | Biallelic insulin receptor (INSR) gene mutations cause congenital syndromes of severe insulin resistance (SIR) known as Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS). At presentation, DS and RMS are difficult to differentiate since they share many clinical features; however, while patients with DS usually die within 1 year of birth, individuals classified as RMS can reach adult age. INSR mutations can be also found in pubertal females with hyperinsulinism, hyperandrogenism, and acanthosis nigricans (type A SIR). We studied the INSR gene in five subjects with congenital SIR and in a patient with type A SIR. Nine biallelic INSR gene mutations (eight novels, including an in-frame deletion of INSR signal peptide) were identified in patients with congenital SIR; a heterozygous, spontaneous INSR mutation was detected in the patient with type A SIR. Two probands, presenting severe hirsutism at birth, died at the age of 3 months and were classified as DS, while other 2, currently 2 and 3 years old, were diagnosed with RMS (patients 3 and 4). The fifth patient with congenital SIR died when 14 months old. Nephrocalcinosis, hyperaldosteronism, hyperreninemia, and hypokalemia, in the absence of hypertension, were discovered in patients 3 and 5 when 24 and 4 months old, respectively. Patient 3, now 3 years/3 months old, still shows hyperreninemic hyperaldosteronism requiring potassium supplementation. We conclude that renal abnormalities resembling antenatal Bartter's syndrome type II, recently reported also by others, is a common observation in patients with congenital SIR. |
| Databáze: | OpenAIRE |
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