To the Editor: Combined immunodeficiency diseases (CID) are a heterogeneous group of disorders which all share profound T cell dysfunction. The presence of autologous T cells complicates diagnosis as these… Click to show full abstract
To the Editor: Combined immunodeficiency diseases (CID) are a heterogeneous group of disorders which all share profound T cell dysfunction. The presence of autologous T cells complicates diagnosis as these exhibit varying degrees of functionality, allowing the patient to survive after the age of 2 years without immunologic reconstitution [1]. Patients with CID suffer from recurrent infections as well as a diverse array of clinical presentations whichmay include lymphoproliferation, immune dysregulation, malignancy, allergy, and organ-specific autoimmunity and/or autoimmune cytopenia [2]. In 2012, serine-threonine protein kinase 4 (STK4) gene deficiency was described by three independent groups as causing autosomal recessive CID characterized by profound CD4 lymphopenia together with recurrent bacterial and viral infections and mucocutaneous candidiasis [3–5]. Immune dysregulation and autoimmune manifestation were also noted. STK4 codes for the ubiquitously expressed mammalian sterile 20-like kinase (MST1), a cytoplasmic protein which demonstrates both proapoptotic and antiapoptotic functions and is known to promote Fas-mediated apoptosis [3–5], as well as inhibiting autoimmunity through modulation of Foxo1 and Foxo3 (Foxo1/3) stability [6]. Here we report a novel stopgain mutation in STK4 in a patient presenting with CID and autoimmune features. In addition, there was an unexpected renal component in the form of a salt-losing tubulopathy suggestive of an acquired Gitelman syndrome, immune complex glomerulonephritis, and Castleman’s-like disease, thereby expanding the phenotypic spectrum associated with loss of this protein. The patient is a 15-year-old female. She was the only child conceived by in vitro fertilization (IVF) pregnancy after 11 years of infertility, to consanguineous parents from Saudi Arabia. Mother suffered from diabetes and systemic lupus erythematosus (SLE) and the pregnancy reached full term. After birth, the patient developed respiratory distress syndrome (RDS) requiring mechanical ventilation and intensive care admission. An atrial septal defect (ASD) was detected after birth which resolved with no surgical intervention. The
               
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