Clinical and Therapeutic Aspects of Sideroblastic Anaemia with B-Cell Immunodeficiency, Periodic Fever and Developmental Delay (SIFD) Syndrome: a Systematic Review

• Published in: Journal of clinical immunology 2023-01, Vol.43 (1), p.1-30
• Main Authors: Maccora, Ilaria, Ramanan, Athimalaipet V., Wiseman, Daniel, Marrani, Edoardo, Mastrolia, Maria V., Simonini, Gabriele
• Format: Article
• Language: English
• Subjects: Anemia, Sideroblastic - complications; Anemia, Sideroblastic - diagnosis; Anemia, Sideroblastic - therapy; Biomedical and Life Sciences; Biomedicine; Child; CME Review; Developmental Disabilities - diagnosis; Developmental Disabilities - therapy; Fever; Humans; Immunologic Deficiency Syndromes - genetics; Immunology; Infectious Diseases; Internal Medicine; Medical Microbiology; Mutation
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-022-01343-0

Background and Purpose Sideroblastic anaemia with B-cell immunodeficiency, periodic fever and developmental delay (SIFD) syndrome is a novel rare autoinflammatory multisystem disorder. We performed a systematic review of the available clinical and therapeutics aspects of the SIFD syndrome. Methods A systematic review according to PRISMA approach, including all articles published before the 30 th of July 2021 in Pubmed and EMBASE database, was performed. Results The search identified 29 publications describing 58 unique patients. To date, 41 unique mutations have been reported. Onset of disease is very early with a median age of 4 months (range 0–252 months). The most frequent manifestations are haematologic such as microcytic anaemia or sideroblastic anaemia (55/58), recurrent fever (52/58), neurologic abnormalities (48/58), immunologic abnormalities in particular a humoral immunodeficiency (48/58), gastrointestinal signs and symptoms (38/58), eye diseases as cataract and retinitis pigmentosa (27/58), failure to thrive (26/58), mucocutaneous involvement (29/58), sensorineural deafness (19/58) and others. To date, 19 patients (35.85%) died because of disease course (16) and complications of hematopoietic cell stems transplantation (3). The use of anti-TNFα and hematopoietic cell stems transplantation (HCST) is dramatically changing the natural history of this disease. Conclusions SIFD syndrome is a novel entity to consider in a child presenting with recurrent fever, anaemia, B-cell immunodeficiency and neurodevelopmental delay. To date, therapeutic guidelines are lacking but anti-TNFα treatment and/or HCST are attractive and might modify the clinical course of this syndrome.