Startseite Novel heterozygous IGF1R mutation in two brothers with developing impaired glucose tolerance
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Novel heterozygous IGF1R mutation in two brothers with developing impaired glucose tolerance

  • Sebastian Burkhardt , Julia Gesing , Thomas M. Kapellen , Peter Kovacs , Jürgen Kratzsch , Marina Schlicke , Heike Stobbe , Anke Tönjes , Jürgen Klammt und Roland Pfäffle EMAIL logo
Veröffentlicht/Copyright: 5. August 2014
Journal of Pediatric Endocrinology and Metabolism
Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 28 Heft 1-2

Abstract

Infants born small for gestational age (SGA) are at risk to develop metabolic complications. Insulin-like growth factor 1 (IGF-1) resistance due to IGF-1 receptor (IGF1R) mutations is a rare genetic condition that causes proportionate growth retardation. The contribution of an impaired IGF1R function to the development of comorbidities such as disturbed glucose homeostasis is not well understood. Genetic analysis and detailed auxological, endocrine and psychological investigations in two male SGA siblings were performed. The two patients and their father bear a novel heterozygous mutation (p.Cys1248Tyr) in the IGF1R gene. Both brothers displayed very similar growth pattern before and during recombinant human growth hormone treatment, whereas oral glucose tolerance tests showed variable manifestations of progressive impaired glucose tolerance. The father had already developed type 2 diabetes mellitus. Growth retardation in our patients is likely caused by the IGF1R mutation that might predispose to disturbances of carbohydrate homeostasis. Therefore, a close metabolic monitoring of affected patients is indicated, particularly if growth hormone therapy is commenced.

Keywords: IGF-1; IGF1R; impaired glucose tolerance; point mutation; rhGH therapy; SGA; short stature
Corresponding author: Roland Pfäffle, Hospital for Children and Adolescents, University of Leipzig, Liebigstr. 20a, 04103 Leipzig, Germany, Phone: +49 3419726331, Fax: +49 3419726349, E-mail:

Acknowledgments

We would like to thank the family of the patients, the physicians in charge Dr. Katrin Naumann and Dr. Hans-Jürgen Lambrecht, Mülsen, Germany, for their cooperation as well as the collaborating medical specialists at the University Hospital Leipzig for their expertise in performing the neuropsychological, auditory and metabolic tests. We also thank Beate Enigk and Ines Müller for her excellent assistance in the preparation and realisation of the genotyping assays. This work was supported by a grant from the Deutsche Forschungsgemeinschaft (Bonn, Germany; project PF 225/3 to JKl and RP).

Conflict of interest statement

Disclosure: R.P. has received research grants from Eli Lilly and Merck Serono, and serves on a Sandoz advisory board.

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Received: 2014-3-23
Accepted: 2014-6-27
Published Online: 2014-8-5
Published in Print: 2015-1-1

©2015 by De Gruyter

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: Childhood Craniopharyngioma
  3. Selected papers from the 3rd International Multidisciplinary Postgraduate Course, April 24–27, 2014
  4. Childhood craniopharyngioma – current status and recent perspectives in diagnostics and treatment
  5. The importance of interdisciplinary communication with patients about complex, chronic illnesses: our experiences as parents of a child with a craniopharyngioma
  6. Adamantinomatous craniopharyngioma: pathology, molecular genetics and mouse models
  7. Endocrine aspects and sequel in patients with craniopharyngioma
  8. Surgery for pediatric craniopharyngiomas: is less more?
  9. Eating behavior, weight problems and eating disorders in 101 long-term survivors of childhood-onset craniopharyngioma
  10. Carbohydrate-lipid profile and use of metformin with micronized fenofibrate in reducing metabolic consequences of craniopharyngioma treatment in children: single institution experience
  11. Effects of T3 treatment on brown adipose tissue and energy expenditure in a patient with craniopharyngioma and hypothalamic obesity
  12. Hypothalamic obesity after treatment for craniopharyngioma: the importance of the home environment
  13. Review article
  14. Association study of TAC3 and TACR3 gene polymorphisms with idiopathic precocious puberty in Chinese girls
  15. Images in pediatric endocrinology
  16. Intestinal invagination in diabetic ketoacidosis: case report
  17. Original articles
  18. Managing incidental findings and disclosure of results in a paediatric research cohort – the LIFE Child Study cohort
  19. The heterogeneity of hyperinsulinaemic hypoglycaemia in 19 patients with Beckwith-Wiedemann syndrome due to KvDMR1 hypomethylation
  20. Gender differences and age-related changes in body fat mass in Tibetan children and teenagers: an analysis by the bioelectrical impedance method
  21. A study of genes involved in adipocyte differentiation
  22. Initiation of growth hormone therapy in idiopathic short stature: do gender differences exist?
  23. The influence of puberty on vitamin D status in obese children and the possible relation between vitamin D deficiency and insulin resistance
  24. Growth failure associated with early neglect: pilot comparison of neglected US children and international adoptees
  25. Effect of growth hormone deficiency on brain MRI findings among children with growth restrictions
  26. Variability of lipid and lipoprotein concentrations during puberty in Brazilian boys
  27. Skin advanced glycation endproducts are elevated at onset of type 1 diabetes in youth
  28. Can optical coherence tomography predict early retinal microvascular pathology in type 1 diabetic adolescents without minimal diabetic retinopathy? A single-centre study
  29. Decreased levels of homoarginine and asymmetric dimethylarginine in children with type 1 diabetes: associations with cardiovascular risk factors but no effect by atorvastin
  30. Influence of catch-up growth on abdominal fat distribution in very low birth weight children – cohort study
  31. Thyrotoxic, hypokalemic periodic paralysis (THPP) in adolescents
  32. Pulmonary function in children with type 1 diabetes mellitus
  33. Identification of deletions in children with congenital hypothyroidism and thyroid dysgenesis with the use of multiplex ligation-dependent probe amplification
  34. Effect of l-thyroxine supplementation on infants with transient hypothyroxinemia of prematurity at 18 months of corrected age: randomized clinical trial
  35. Vitamin D-containing supplements for children between 1–3 years of age: Are they essential for bone health?
  36. Anti-Mullerian hormone levels in American girls by age and race/ethnicity
  37. The effect of tailoring of cornstarch intake on stature in children with glycogen storage disease type III
  38. Thyroid disease in Chinese girls with Turner syndrome
  39. Patient reports
  40. Pure gonadal dysgenesis (Swyer syndrome) due to microdeletion in the SRY gene: a case report
  41. Hypophosphatemic rickets caused by a novel splice donor site mutation and activation of two cryptic splice donor sites in the PHEX gene
  42. Novel heterozygous IGF1R mutation in two brothers with developing impaired glucose tolerance
  43. A case of pediatric ectopic thyroid in lateral lymph nodes
  44. Hyperostosis-hyperphosphatemia syndrome (HHS): report of two cases with a recurrent mutation and review of the literature
  45. Needle detachment from the Sure-T® infusion set in two young children with diabetes mellitus (DM) treated with continuous subcutaneous insulin infusion (CSII) and unexplained hyperglycaemia
  46. Familial dysalbuminemic hyperthyroxinemia in a 4-year-old girl with hyperactivity, palpitations and advanced dental age: how gold standard assays may be misleading
https://doi.org/10.1515/jpem-2014-0132
Schlagwörter für diesen Artikel
IGF-1; IGF1R; impaired glucose tolerance; point mutation; rhGH therapy; SGA; short stature

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: Childhood Craniopharyngioma
  3. Selected papers from the 3rd International Multidisciplinary Postgraduate Course, April 24–27, 2014
  4. Childhood craniopharyngioma – current status and recent perspectives in diagnostics and treatment
  5. The importance of interdisciplinary communication with patients about complex, chronic illnesses: our experiences as parents of a child with a craniopharyngioma
  6. Adamantinomatous craniopharyngioma: pathology, molecular genetics and mouse models
  7. Endocrine aspects and sequel in patients with craniopharyngioma
  8. Surgery for pediatric craniopharyngiomas: is less more?
  9. Eating behavior, weight problems and eating disorders in 101 long-term survivors of childhood-onset craniopharyngioma
  10. Carbohydrate-lipid profile and use of metformin with micronized fenofibrate in reducing metabolic consequences of craniopharyngioma treatment in children: single institution experience
  11. Effects of T3 treatment on brown adipose tissue and energy expenditure in a patient with craniopharyngioma and hypothalamic obesity
  12. Hypothalamic obesity after treatment for craniopharyngioma: the importance of the home environment
  13. Review article
  14. Association study of TAC3 and TACR3 gene polymorphisms with idiopathic precocious puberty in Chinese girls
  15. Images in pediatric endocrinology
  16. Intestinal invagination in diabetic ketoacidosis: case report
  17. Original articles
  18. Managing incidental findings and disclosure of results in a paediatric research cohort – the LIFE Child Study cohort
  19. The heterogeneity of hyperinsulinaemic hypoglycaemia in 19 patients with Beckwith-Wiedemann syndrome due to KvDMR1 hypomethylation
  20. Gender differences and age-related changes in body fat mass in Tibetan children and teenagers: an analysis by the bioelectrical impedance method
  21. A study of genes involved in adipocyte differentiation
  22. Initiation of growth hormone therapy in idiopathic short stature: do gender differences exist?
  23. The influence of puberty on vitamin D status in obese children and the possible relation between vitamin D deficiency and insulin resistance
  24. Growth failure associated with early neglect: pilot comparison of neglected US children and international adoptees
  25. Effect of growth hormone deficiency on brain MRI findings among children with growth restrictions
  26. Variability of lipid and lipoprotein concentrations during puberty in Brazilian boys
  27. Skin advanced glycation endproducts are elevated at onset of type 1 diabetes in youth
  28. Can optical coherence tomography predict early retinal microvascular pathology in type 1 diabetic adolescents without minimal diabetic retinopathy? A single-centre study
  29. Decreased levels of homoarginine and asymmetric dimethylarginine in children with type 1 diabetes: associations with cardiovascular risk factors but no effect by atorvastin
  30. Influence of catch-up growth on abdominal fat distribution in very low birth weight children – cohort study
  31. Thyrotoxic, hypokalemic periodic paralysis (THPP) in adolescents
  32. Pulmonary function in children with type 1 diabetes mellitus
  33. Identification of deletions in children with congenital hypothyroidism and thyroid dysgenesis with the use of multiplex ligation-dependent probe amplification
  34. Effect of l-thyroxine supplementation on infants with transient hypothyroxinemia of prematurity at 18 months of corrected age: randomized clinical trial
  35. Vitamin D-containing supplements for children between 1–3 years of age: Are they essential for bone health?
  36. Anti-Mullerian hormone levels in American girls by age and race/ethnicity
  37. The effect of tailoring of cornstarch intake on stature in children with glycogen storage disease type III
  38. Thyroid disease in Chinese girls with Turner syndrome
  39. Patient reports
  40. Pure gonadal dysgenesis (Swyer syndrome) due to microdeletion in the SRY gene: a case report
  41. Hypophosphatemic rickets caused by a novel splice donor site mutation and activation of two cryptic splice donor sites in the PHEX gene
  42. Novel heterozygous IGF1R mutation in two brothers with developing impaired glucose tolerance
  43. A case of pediatric ectopic thyroid in lateral lymph nodes
  44. Hyperostosis-hyperphosphatemia syndrome (HHS): report of two cases with a recurrent mutation and review of the literature
  45. Needle detachment from the Sure-T® infusion set in two young children with diabetes mellitus (DM) treated with continuous subcutaneous insulin infusion (CSII) and unexplained hyperglycaemia
  46. Familial dysalbuminemic hyperthyroxinemia in a 4-year-old girl with hyperactivity, palpitations and advanced dental age: how gold standard assays may be misleading
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