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

J Clin Immunol. 2023 Jan;43(1):1-30. doi: 10.1007/s10875-022-01343-0. Epub 2022 Aug 19.


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 30th 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.

Keywords: Autoinflammatory disease; Etanercept; Immunodeficiency; Recurrent fever; SIFD; Sideroblastic anaemia.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Anemia, Sideroblastic* / complications
  • Anemia, Sideroblastic* / diagnosis
  • Anemia, Sideroblastic* / therapy
  • Child
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / therapy
  • Fever
  • Humans
  • Immunologic Deficiency Syndromes* / genetics
  • Mutation