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

作者：Burkhardt Sebastian; Gesing Julia; Kapellen Thomas M; Kovacs Peter; Kratzsch Juergen; Schlicke Marina; Stobbe Heike; Toenjes Anke; Klammt Juergen; Pfaeffle Roland

来源：Journal of Pediatric Endocrinology & Metabolism, 2015, 28(1-2): 217-225.

DOI：10.1515/jpem-2014-0132

• IGF-1
• IGF1R
• impaired glucose tolerance
• point mutation
• rhGH therapy
• SGA
• short stature

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.

• 出版日期2015-1