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

Overview

Journal J Clin Immunol

Publisher Springer

Specialty Allergy & Immunology

Date 2022 Aug 19

PMID 35984545

Authors

Ilaria Maccora

Athimalaipet V Ramanan

Daniel Wiseman

Edoardo Marrani

Maria V Mastrolia

Gabriele Simonini

Affiliations

Soon will be listed here.

Abstract

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 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.

Citing Articles

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Case report: Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay: Three cases and a literature review.

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References

Wedatilake Y, Niazi R, Fassone E, Powell C, Pearce S, Plagnol V . TRNT1 deficiency: clinical, biochemical and molecular genetic features. Orphanet J Rare Dis. 2016; 11(1):90. PMC: 4930608. DOI: 10.1186/s13023-016-0477-0. View

Orlando F, Naddei R, Stellacci E, Gallinoro C, Melis D, Tartaglia M . Etanercept as a successful therapy in autoinflammatory syndrome related to TRNT1 mutations: a case-based review. Clin Rheumatol. 2021; 40(10):4341-4348. DOI: 10.1007/s10067-021-05653-3. View

Hull S, Malik A, Arno G, Mackay D, Plagnol V, Michaelides M . Expanding the Phenotype of TRNT1-Related Immunodeficiency to Include Childhood Cataract and Inner Retinal Dysfunction. JAMA Ophthalmol. 2016; 134(9):1049-53. DOI: 10.1001/jamaophthalmol.2015.5833. View

Barton C, Kausar S, Kerr D, Bitetti S, Wynn R . SIFD as a novel cause of severe fetal hydrops and neonatal anaemia with iron loading and marked extramedullary haemopoiesis. J Clin Pathol. 2017; 71(3):275-278. PMC: 5868532. DOI: 10.1136/jclinpath-2017-204698. View

Fremond M, Melki I, Kracker S, Bondet V, Duffy D, Rice G . Comment on: 'Aberrant tRNA processing causes an autoinflammatory syndrome responsive to TNF inhibitors' by Giannelou : mutations in result in a constitutive activation of type I interferon signalling. Ann Rheum Dis. 2018; 78(8):e86. DOI: 10.1136/annrheumdis-2018-213745. View

Bardou M, Rivitti-Machado M, Michalany N, de Jesus A, Goldbach-Mansky R, Barros J . Neutrophilic dermatosis: a new skin manifestation and novel pathogenic variant in a rare autoinflammatory disease. Australas J Dermatol. 2020; 62(2):e276-e279. DOI: 10.1111/ajd.13527. View

Sasarman F, Thiffault I, Weraarpachai W, Salomon S, Maftei C, Gauthier J . The 3' addition of CCA to mitochondrial tRNASer(AGY) is specifically impaired in patients with mutations in the tRNA nucleotidyl transferase TRNT1. Hum Mol Genet. 2015; 24(10):2841-7. PMC: 4406295. DOI: 10.1093/hmg/ddv044. View

DeLuca A, Whitmore S, Barnes J, Sharma T, Westfall T, Scott C . Hypomorphic mutations in TRNT1 cause retinitis pigmentosa with erythrocytic microcytosis. Hum Mol Genet. 2015; 25(1):44-56. PMC: 4690490. DOI: 10.1093/hmg/ddv446. View

Rigante D, Stellacci E, Leoni C, Onesimo R, Radio F, Pizzi S . Biallelic TRNT1 variants in a child with B cell immunodeficiency, periodic fever and developmental delay without sideroblastic anemia (SIFD variant). Immunol Lett. 2020; 225:64-65. DOI: 10.1016/j.imlet.2020.06.012. View

10.

Jfri A, El-Helou T, Watters K, Belisle A, Litvinov I, Netchiporouk E . Congenital sideroblastic anemia associated with B cell immunodeficiency, periodic fevers, and developmental delay: A case report and review of mucocutaneous features. SAGE Open Med Case Rep. 2019; 7:2050313X19876710. PMC: 6747858. DOI: 10.1177/2050313X19876710. View

11.

Papa R, Picco P, Gattorno M . The expanding pathways of autoinflammation: a lesson from the first 100 genes related to autoinflammatory manifestations. Adv Protein Chem Struct Biol. 2020; 120:1-44. DOI: 10.1016/bs.apcsb.2019.11.001. View

12.

Chakraborty P, Schmitz-Abe K, Kennedy E, Mamady H, Naas T, Durie D . Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). Blood. 2014; 124(18):2867-71. PMC: 4215314. DOI: 10.1182/blood-2014-08-591370. View

13.

Frans G, Moens L, Schaballie H, Wuyts G, Liston A, Poesen K . Homozygous N-terminal missense mutation in TRNT1 leads to progressive B-cell immunodeficiency in adulthood. J Allergy Clin Immunol. 2016; 139(1):360-363.e6. DOI: 10.1016/j.jaci.2016.06.050. View

14.

Wiseman D, May A, Jolles S, Connor P, Powell C, Heeney M . A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Blood. 2013; 122(1):112-23. PMC: 3761334. DOI: 10.1182/blood-2012-08-439083. View

15.

Leibovitch M, Hanic-Joyce P, Joyce P . In vitro studies of disease-linked variants of human tRNA nucleotidyltransferase reveal decreased thermal stability and altered catalytic activity. Biochim Biophys Acta Proteins Proteom. 2018; 1866(4):527-540. DOI: 10.1016/j.bbapap.2018.02.002. View

16.

Maccora I, Ramanan A, Vergnano S, Roderick M . Sideroblastic anaemia, immunodeficiency, periodic fevers and developmental delay (SIFD) presenting as systemic inflammation with arthritis. Rheumatology (Oxford). 2021; 60(7):e234-e236. DOI: 10.1093/rheumatology/keab010. View

17.

Maccora I, Frongia I, Azzari C, Ricci S, Cimaz R, Simonini G . A misleading case of deficiency of adenosine deaminase 2 (DADA2): the magnifying glass of the scientific knowledge drives the tailored medicine in real life. Clin Exp Rheumatol. 2018; 36(6 Suppl 115):146. View

18.

Maccora I, Marrani E, Mastrolia M, Abu-Rumeileh S, Maniscalco V, Fusco E . Ocular involvement in monogenic autoinflammatory disease. Autoimmun Rev. 2021; 20(11):102944. DOI: 10.1016/j.autrev.2021.102944. View

19.

Hoang T, Albert D . Novel presentations of periodic fever syndromes: Discrepancies between genetic and clinical diagnoses. Eur J Rheumatol. 2018; 6(1):12-18. PMC: 6459325. DOI: 10.5152/eurjrheum.2018.18023. View

20.

Christiansen M, Offersen R, Jensen J, Petersen M, Larsen C, Mogensen T . Identification of Novel Genetic Variants in CVID Patients With Autoimmunity, Autoinflammation, or Malignancy. Front Immunol. 2020; 10:3022. PMC: 6996488. DOI: 10.3389/fimmu.2019.03022. View