Management of Chronic Immune Thrombocytopenia and Presumed Autoimmune Hepatitis in a Child with IKAROS Haploinsufficienc
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LETTER TO EDITOR
Management of Chronic Immune Thrombocytopenia and Presumed Autoimmune Hepatitis in a Child with IKAROS Haploinsufficiency Daniel J. Groth 1 & Madhavi M. Lakkaraja 2,3 & Johanna O. Ferreira 4 & Elizabeth J. Feuille 5 & Jennifer A. Bassetti 6 & Shipra M. Kaicker 2 Received: 27 August 2019 / Accepted: 1 April 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Keywords IKAROS . immune thrombocytopenia (ITP) . rituximab . autoimmune hepatitis
To the Editor, IKAROS, a transcription factor encoded by the IKAROS family zinc finger protein 1 (IKZF1) gene, is crucial for hematopoiesis and B cell development [1]. Somatic IKZF1 pathogenic variants have long been associated with B cell precursor acute lymphoblastic leukemia (BCP-ALL) [1, 2]. In recent studies, heterozygous germline IKZF1 pathogenic variants causing haploinsufficiency have been identified in patients with a B cell immunodeficiency mimicking common variable immunodeficiency (CVID) with young adult onset, inherited in an autosomal dominant manner with incomplete penetrance [3–7]. These patients suffer progressive B cell defects caused by aberrant development of common lymphoid progenitors [4]. Some have quantitative changes in T cell subsets [3, 4]. More recently, de novo heterozygous dominant negative germline mutations in the DNA-binding domain of IKZF1
* Shipra M. Kaicker [email protected] 1
Department of Pediatrics, New York Presbyterian Hospital/Weill Cornell Medical College, 525 E 68th St, New York, NY 10065, USA
2
Division of Pediatric Hematology and Oncology, New York Presbyterian Hospital/Weill Cornell Medical College, 525 East 68th Street, Payson-695, New York, NY 10065, USA
3
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
4
Division of Pediatric Gastroenterology and Nutrition, New York Presbyterian Hospital/Weill Cornell Medical College, 505 East 70th Street, Helmsley Tower, 3rd Floor, New York, NY 10021, USA
5
Division of Pediatric Pulmonology, Allergy & Immunology, New York Presbyterian Hospital/Weill Cornell Medical College, 505 East 70th Street, Helmsley Tower, 3rd Floor, New York, NY 10021, USA
6
Division of Clinical Genetics, New York Presbyterian Hospital/Weill Cornell Medical College, 505 East 70th Street, Helmsley Tower, 3rd Floor, New York, NY 10021, USA
(affecting amino acid N159S or T) have been identified in patients with a combined immunodeficiency (CID) [8]. This more severe IKAROS deficiency causes a defect in memory T and B cells and has onset in the first months of life with opportunistic infections. Here we present the case of a child with history of BCP-ALL, immune thrombocytopenia (ITP), and presumed autoimmune hepatitis in whom identification of a germline IKZF1 mutation (p.R162W) associated with haploinsufficiency guided management decisions to achieve remission of her previously treatment-refractory chronic ITP.
Case Description The patient is a 7-year-old female who initially came to medical attention when
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