Ruxolitinib Controls Lymphoproliferation and Diabetes in a STAT3-GOF Patient
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LETTER TO EDITOR
Ruxolitinib Controls Lymphoproliferation and Diabetes in a STAT3-GOF Patient Oliver Wegehaupt 1,2
&
Tina Muckenhaupt 3 & Matthew B Johnson 4 & Karl Otfried Schwab 5 & Carsten Speckmann 1,2
Received: 30 June 2020 / Accepted: 4 September 2020 / Published online: 17 September 2020 # The Author(s) 2020
To the Editor We report on a 2 9-/12-year-old male with STAT3-GOF mutation, whose exacerbation of neonatal-onset diabetes, lymphoproliferation, and autoinflammation was successfully treated with ruxolitinib. The patient was born at term as the first child of nonconsanguineous Caucasian parents and developed an insulindependent diabetes (IDDM) at the age of 3 months, initially presenting with polydipsia, fatigue, and vomiting. Laboratory findings showed pronounced ketoacidosis (pH 7.09; pCO2 28 mmHg, base excess − 25 mmol/l; ketone 4.9 mmol/l; blood glucose 32.3 mmol/l; HbA1c 5.6%; C-peptide 0.05 nmol/l; insulin 1.3 mU/l). Clinical investigation and initial abdominal ultrasound were unremarkable, i.e., without signs of lymphoproliferation. Ahead of diabetes therapy, insulin-autoantibodies (IAA; 20.6 U/ml) and glutamate-decarboxylase autoantibodies (antiGAD; 1.1 kU/l) were positive. Genetic testing, initiated because of neonatal-onset IDDM, did not reveal any variants in KCNJ11, ABCC8, or INS. At initial discharge, the child was provided with Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10875-020-00864-w) contains supplementary material, which is available to authorized users. * Carsten Speckmann [email protected] 1
Faculty of Medicine, Center for Pediatrics and Adolescent Medicine, Medical Center, University of Freiburg, Mathildenstr 1, 79106 Freiburg, Germany
2
Faculty of Medicine, Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Institute for Immunodeficiency, University of Freiburg, Freiburg, Germany
3
Diabetes Centre, Center for Pediatrics and Adolescent Medicine, Reutlingen, Germany
4
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK
5
Faculty of Medicine, Center for Pediatrics and Adolescent Medicine, Division of Pediatric Diabetes, Medical Center, University of Freiburg, Freiburg, Germany
sensor-assisted pump therapy and showed a moderate daily insulin demand of 0.5 IE/kg/day. Between the age of 14 and 17 months, the patient developed additional autoimmune phenomena with progressive panniculitis at the anterior feet and accompanying lymphedema and lymphangitis (Fig. 1a). Additionally, marked inguinal lymphoproliferation was noted. Blood counts remained unremarkable. The child developed lipoatrophic skin lesions in areas where insulin was injected subcutaneously. At the age of 17 months, further genetic testing at the University of Exeter, which included 26 known genetic causes of neonatal diabetes (Twist BioScience custom targeted panel, Illumina NextSeq), identified a known pathogenic heterozygous gain-of-function (GOF) variant in STAT3
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