Abstract | AIM: METHODS: Mutations were looked for in the insulin receptor gene of a four-month-old female baby with leprechaunism. The patient's skin fibroblasts were analyzed for response to insulin and IGF1. At the clinical level, the very long-term effects of treatment with rhIGF1/rhIGFBP3 were evaluated by clinical and metabolic parameters. RESULTS: The patient's diagnosis was based on compound heterozygous mutations in two alleles of the insulin receptor gene, thus confirming leprechaunism. Cultured fibroblasts showed a decreased number of insulin receptors and were insulin-resistant. However, IGF1 was able to stimulate IGF1 receptor signalling, suggesting possible activation of a salvage pathway. Treatment with IGF1/IGFBP3 for 8.7 years, then IGF1 for 2 years, resulted in normalization of circulating levels of IGF1 and IGFBP3. Large daily variations in glycaemia and insulinaemia persisted, but mean glycaemia decreased. Regarding growth, the patient's BMI Z score normalized and length/height score improved. Our patient presented normal neurological development and academic achievement. The treatment was free of adverse effects. CONCLUSION: Our results provide evidence that rhIGF1 with and without rhIGFBP3 can prevent fatal outcomes, and improve growth and metabolic parameters, for more than 10 years in a patient with leprechaunism. Long-term rhIGF1 for severe insulin resistance syndrome should be considered.
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Authors | M de Kerdanet, M Caron-Debarle, S Nivot, T Gaillot, O Lascols, B Fremont, M Bonaure, S Gie, C Massart, J Capeau |
Journal | Diabetes & metabolism
(Diabetes Metab)
Vol. 41
Issue 4
Pg. 331-337
(09 2015)
ISSN: 1878-1780 [Electronic] France |
PMID | 25465274
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Antigens, CD
- Recombinant Proteins
- Insulin-Like Growth Factor I
- INSR protein, human
- Receptor, Insulin
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Topics |
- Antigens, CD
(genetics)
- Child
- Child Development
(drug effects)
- Child, Preschool
- Donohue Syndrome
(drug therapy, genetics, metabolism, physiopathology)
- Female
- Follow-Up Studies
- Hormone Replacement Therapy
- Humans
- Infant
- Insulin Resistance
(genetics)
- Insulin-Like Growth Factor I
(metabolism, therapeutic use)
- Mutation
- Receptor, Insulin
(genetics)
- Recombinant Proteins
(therapeutic use)
- Treatment Outcome
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