Abstract
Costello syndrome is characterized by facial dysmorphia, hyperpigmented skin, palmar and plantar hyperkeratosis, curly hair, perioral and nasal papillomata (more rarely localized anally and on vocal cords), short stature, mental retardation and sociable personality. Although growth retardation is typical of Costello syndrome, its cause is not defined. We report on a 10-yr-old Caucasian girl affected by Costello syndrome with fasting hypoglycemia and short stature, associated low circulating levels of acid-labile subunit (ALS), relatively low levels of IGF-I and IGFBP-3, and normal IGF-II, mostly circulating in a binary complex with IGFBP-2 and -6 instead of in a 150 kDa ternary complex. The reduced ALS concentration and the consequent impaired formation of the circulating 150 kDa ternary complex can induce an accelerated clearance rate of IGF peptides and of IGFBP-3, contributing to the decreased IGF-I growth promoting activity in our patient. Moreover, the presence of IGF-II in the binary complex, which has been postulated to increase the insulin-like effects of these peptides, can explain, at least in part, the patient’s asymptomatic fasting hypoglycemia. (J. Endocrinol. Invest. 29: 261–264, 2006)
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References
Costello JM. A new syndrome: Mental subnormality and nasal papillomata. Aust Paediatr J 1977, 13: 114–8.
Der Kalousian V.M., Moroz B., McIntosh N., Watters K., Blaichman S. Costello syndrome. Am J Med Genet 1991, 4: 69–73.
Zampino G, Mostroiacovo P, Ricci R, et al. Costello syndrome: further clinical delineation, natural history, genetic definition, and nosology. Am J Med Genet 1993, 47: 176–83.
Borochowitz Z, Pavone L, Mazor G, Rizzo R, Dar H. New multiple congenital anomalies: mental retardation syndrome (MCA/MR) with facio-cutaneous-skeletal involvement. Am J Med Genet 1992, 43: 678–85.
Lurie IW. Genetics of the Costello syndrome. Am J Med Genet 1994, 52: 358–9.
Johnson JP, Golabi M, Norton ME, et al. Costello syndrome: Phenotype, natural history, differential diagnosis, and possible cause. J Pediatr 1998, 133: 441–8.
Okamoto N, Chiyo H, Imai K, Otani K, Futagi Y. A Japanese patient with the Costello syndrome. Hum Genet 1994, 93: 605–6.
Legault L, Gagnon C, Lapointe N. Growth hormone deficiency in Costello syndrome: A possible explanation for the short stature. J Pediatr 2001, 138: 151–2.
Di Rocco M, Gatti R, Gandullia P, Barabino A, Picco P, Borrone C. Report on two patients with Costello syndrome and sialuria. Am J Med Genet 1993, 47: 1135–40.
Baxter RC, Martin JL, Beniac VA. High molecular weight insulin-like growth factor binding protein complex. Purification and properties of the acid-labile subunit from human serum. J Biol Chem 1989, 264: 11843–8.
Barreca A, Ponzani P, Arvigo M, Giordano G, Minuto F. Effect of the acid-labile subunit on the binding of insulin-like growth factor (IGF)-binding protein-3 to [125I]IGF-I. J Clin Endocrinol Metab 1995, 80: 1318–24.
Zapf J, Schmid C, Froesch ER. Biological and immunological properties of insulin-like growth factors I and II. J Clin Endocrinol Metab 1984, 13: 3–30.
Arosio M, Garrone S, Bruzzi P, Faglia G, Minuto F, Barreca A. Diagnostic value of the acid-labile subunit (ALS) in acromegaly. Evaluation in comparison with insulin-like growth factor (IGF)-I, and IGF binding proteins (IGFBP-1, -2, -and -3). J Clin Endocrinol Metab 2001, 86: 1091–8.
Jones J, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 1995, 16: 3–34.
Zapf J, Hauri C, Futo E, et al. Intravenously injected insulin-like growth factor (IGF) I/GF binding protein-3 complex exerts insulin-like effects in hypophysectomized, but not in normal rats. J Clin Invest 1995, 95: 179–86.
Fielder PJ, Mortensen DL, Mallet P, Carlsson B, Baxter RC, Clark RG. Differential long-term effects of insulin-like growth factor-I (IGF-I) growth hormone (GH), and IGF-I plus GH on body growth and IGF binding proteins in hypophysectomized rats. Endocrinology 1996, 137: 1913–20.
Murphy LJ, Molnar P, Lu X, Huang H Expression of human insulin-like growth factor binding protein-3 in transgenic mice]. J Mol Endocrinol 1995, 15: 293–303
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Barreca, A., Cotellessa, M., Boschetti, M. et al. The IGF system in a case of Costello syndrome. J Endocrinol Invest 29, 261–264 (2006). https://doi.org/10.1007/BF03345551
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DOI: https://doi.org/10.1007/BF03345551