Fanconi Anemia and Laron Syndrome

• Published in: The American journal of the medical sciences 2017-05, Vol.353 (5), p.425-432
• Main Authors: Castilla-Cortazar, Inma, MD, PhD, de Ita, Julieta Rodriguez, MD, PhD, Aguirre, Gabriel Amador, MSc, Castorena-Torres, Fabiola, PhD, Ortiz-Urbina, Jesús, MD, García-Magariño, Mariano, PhD, de la Garza, Rocío García, MD, PhD, Diaz Olachea, Carlos, MD, Elizondo Leal, Martha Irma, PhD
• Format: Article
• Language: English
• Subjects: Body Height; Developmental disorders; Endocrine disorders; Fanconi anemia; Fanconi Anemia - complications; Fanconi Anemia - genetics; Female; Human Growth Hormone - blood; Humans; IGF-1; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor I - metabolism; Internal Medicine; Laron syndrome; Laron Syndrome - complications; Laron Syndrome - genetics; Laron Syndrome - pathology; Mexico; Receptors, Somatotropin - blood; Signal Transduction; Young Adult
• ISSN: 0002-9629; 1538-2990
• DOI: 10.1016/j.amjms.2017.02.001

Abstract Background Fanconi anemia (FA) is a condition characterized by genetic instability and short stature, which is due to growth hormone (GH) deficiency in most cases. However, no apparent relationships have been identified between FA complementation group genes and GH. In this study, we thereby considered an association between FA and Laron syndrome (LS) (insulin-like growth factor 1 [IGF-1] deficiency). Methods A 21-year-old female Mexican patient with a genetic diagnosis of FA was referred to our research department for an evaluation of her short stature. Upon admission to our facility, her phenotype led to a suspicion of LS; accordingly, serum levels of IGF-1 and IGF binding protein 3 were analyzed and a GH stimulation test was performed. In addition, we used a next-generation sequencing approach for a molecular evaluation of FA disease-causing mutations and genes involved in the GH-IGF signaling pathway. Results Tests revealed low levels of IGF-1 and IGF binding protein 3 that remained within normal ranges, as well as a lack of response to GH stimulation. Sequencing confirmed a defect in the GH receptor signaling pathway. Conclusions To the best of our knowledge, this study is the first to suggest an association between FA and LS. We propose that IGF-1 administration might improve some FA complications and functions based upon IGF-1 beneficial actions observed in animal, cell and indirect clinical models: erythropoiesis modulation, immune function improvement and metabolic regulation.