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

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 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.

Spontaneous, simultaneous bilateral osteonecrosis of the femoral heads in a patient with sideroblastic anaemia with B-cell immunodeficiency, periodic fever and developmental delay syndrome

“…The exact pathogenesis is under study but many clinical signs may be linked to oxidative phosphorylation (OXPHOS) defects and dysfunctional translation, particularly in the mitochondria 5 6. Thus far, 58 patients with SIFD have been described: the syndrome is notable for the diversity of phenotypes, with siblings bearing the same mutations having different clinical presentations 1 2 5 7–31…”

Case report: Muscle involvement in a Chinese patient with TRNT1-related disorder

“…Clinical phenotypes associated with TRNT1 include autosomal recessive sideroblastic anemia with B-cell immunodeficiency, periodic fever, and developmental delay (SIFD, OMIM: 616084), and retinitis pigmentosa with erythrocytic microcytosis (OMIM: 616959). Till now, a total of 58 patients with SIFD and 41 mutations have been reported (4). SIFD is a autoinflammatory multisystem disorder, and the phenotypic spectrum is still emerging, with some specific common features but a diverse set of clinical phenotypes and patterns of system involvement described, thus it would be more appropriate to consider this syndrome as a TRNT1-related disorder (4).…”

TRNT-1 Deficiency Is Associated with Loss of tRNA Integrity and Imbalance of Distinct Proteins

“…Subsequent publications have revealed significant clinical heterogeneity of disease associated with TRNT1 deficiency. In a recent systematic review, 41 unique mutations have been noted in 58 individual cases [8]. SIFD is predominantly characterized by severe sideroblastic anemia (SA) or microcytic anemia and very early onset in the neonatal period or infancy with a median age of 4 months (range 0-252 months), although a broad range of additional variable clinical features is present [2,8].…”