Endocrine Abstracts

Introduction: STAT5 proteins are components of the common growth hormone and interleukin-2 family of cytokine signaling pathway which is a critical molecule involved in growth hormone receptor (GHR) signal transduction, mediating the growth-promoting actions of the GHR. In addition to its role in GHR signal transduction, STAT5B is also involved in the immune system as an important mediator of interleukin-2 action and disruption of this signal transduction is responsible for T-cell function defects. Recently, there have been case reports on rare homozygous mutations in the signal transducer and activator of transcription 5B gene in patients with growth hormone insensitivity (GHI). We report a case of a 13-year-old female child who presented with short stature and recurrent chest infections whose evaluation revealed STAT5B missense variant.

Case report: A 13-year-old girl born of non-consanguineous marriage was referred to tertiary center in view of mildly elevated serum TSH levels. She had severe growth retardation, eczema along with chronic respiratory disease and features of chronic diarrhea on clinical evaluation. Because of the prolonged history of recurrent infections, chronic lung disease, and severe growth retardation, immunodeficiency and GH deficiency or insensitivity was suspected. Her basal GH level was normal and IGF1 serum levels were extremely low. Hypothalamic–pituitary magnetic resonance imaging was normal. Moderate lymphopenia was observed with a reduced number of all evaluated cell lines. The levels of immunoglobulins were within the normal limits. Molecular analysis revealed homozygous missense variant of STAT5B gene which prognosticates probably damaging by bioinformatics techniques.

Conclusion: In summary, the presence of short stature in a child with chronic respiratory difficulties and immune dysfunction suggests growth hormone deficiency due to STAT5B pathological variants. Clinical and investigational dissociation for growth hormone deficiency associated with immunological defects are strongly suggestive of a mutation in STAT5B gene and should trigger an investigation for defects in this gene.