A Rare Autoinflammatory Disorder in a Pediatric Patient with Favorable Response to Etanercept: Sideroblastic Anemia with B Cell Immunodeficiency, Periodic Fevers, and Developmental Delay Syndrome

Ekinci, Rabia Miray Kışla; Zararsiz, Aslıhan; Demir, Gizem Ürel; Anlaş, Özlem

doi:10.1089/ped.2022.0090

Cited by 3 publications

(1 citation statement)

References 12 publications

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“…Corticosteroid therapy has achieved only a partial response in patients with SIFD [ 6 – 10 , 17 , 25 , 26 , 32 ], which is similar to our findings in patient 2. Corticosteroids may not be first-line therapy for SIFD due to their weak efficacy and serious side-effects.…”

Section: Discussionsupporting

confidence: 90%

Thalidomide as an Effective Treatment in Sideroblastic Anemia, Immunodeficiency, Periodic Fevers, and Developmental Delay (SIFD)

Deng

Han

et al. 2023

J Clin Immunol

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Purpose Sideroblastic anemia, immunodeficiency, periodic fevers, and developmental delay (SIFD) is an autosomal recessive syndrome caused by biallelic loss-of-function variant of tRNA nucleotidyl transferase 1 (TRNT1). Efficacious methods to treat SIFD are lacking. We identified two novel mutations in TRNT1 and an efficacious and novel therapy for SIFD. Methods We retrospectively summarized the clinical records of two patients with SIFD from different families and reviewed all published cases of SIFD. Results Both patients had periodic fever, developmental delay, rash, microcytic anemia, and B cell lymphopenia with infections. Whole-exome sequencing of patient 1 identified a previously unreported homozygous mutation of TRNT1 (c.706G > A/p.Glu236Lys). He received intravenous immunoglobulin (IVIG) replacement and antibiotics, but died at 1 year of age. Gene testing in patient 2 revealed compound heterozygous mutations (c.907C > G/p.Gln303Glu and c.88A > G/p.Met30Val) in TRNT1, the former of which is a novel mutation. Periodic fever was controlled in the first month after adalimumab therapy and IVIG replacement, but recurred in the second month. Adalimumab was discontinued and replaced with thalidomide, which controlled the periodic fever and normalized inflammatory markers effectively. A retrospective analysis of reported cases revealed 69 patients with SIFD carrying 46 mutations. The male: female ratio was 1: 1, and the mean age of onset was 3.0 months. The most common clinical manifestations in patients with SIFD were microcytic anemia (82.6%), hypogammaglobulinemia/B cell lymphopenia (75.4%), periodic fever (66.7%), and developmental delay (60.0%). In addition to the typical tetralogy, SIFD features several heterogeneous symptoms involving multiple systems. Corticosteroids, immunosuppressants, and anakinra have low efficacy, whereas etanercept suppressed fever and improved anemia in reports. Bone-marrow transplantation can be used to treat severe SIFD, but carries a high risk. In total, 28.2% (20/71) of reported patients died, mainly because of multi-organ failure. Biallelic mutations located in exon1-intron5 lead to more severe phenotypes and higher mortality. Furthermore, 15.5% (11/71) patients survived to adulthood. The symptoms could be resolved spontaneously in five patients. Conclusions Thalidomide can control the inflammation of SIFD and represents a new treatment for SIFD.

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Section: Discussionsupporting

confidence: 90%

Thalidomide as an Effective Treatment in Sideroblastic Anemia, Immunodeficiency, Periodic Fevers, and Developmental Delay (SIFD)

Deng

Han

et al. 2023

J Clin Immunol

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Colchicine

2022

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

Chen

Fu²,

Mo³

et al. 2023

Front. Pediatr.

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Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) is a serious autosomal recessive syndrome caused by biallelic mutations in cytosine–cytosine–adenosine tRNA nucleotidyltransferase 1 (TRNT1). The main clinical features of SIFD are periodic fevers, developmental delay, sideroblastic or microcytic anemia, and immunodeficiency. Herein, we report three cases of SIFD with compound heterozygous variants of TRNT1. Patients 1 and 2 were siblings; they presented with periodic fevers, arthritis, low immunoglobulin A, bilateral cataracts, anemia, and neurodevelopmental and developmental delay. Patient 3 had severed clinical features with recurrent fever and infections. She was treated with infliximab and symptomatic treatments but without therapeutic effect. She received a stem cell transplantation of umbilical cord blood but died of posttransplant infection and posttransplant graft-vs.-host disease 17 days after transplantation. Finally, a literature review revealed that TRNT1 variants differed among SIFD patients. Our cases and literature review further expand existing knowledge on the phenotype and TRNT1 variations of SIFD and suggest that the early genomic diagnosis of TRNT1 is valuable to promptly assess bone marrow transplantation and tumor necrosis factor inhibitor treatments, which might be effective for the immunodeficiency and inflammation caused by SIFD.

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A Rare Autoinflammatory Disorder in a Pediatric Patient with Favorable Response to Etanercept: Sideroblastic Anemia with B Cell Immunodeficiency, Periodic Fevers, and Developmental Delay Syndrome

Cited by 3 publications

References 12 publications

Thalidomide as an Effective Treatment in Sideroblastic Anemia, Immunodeficiency, Periodic Fevers, and Developmental Delay (SIFD)

Thalidomide as an Effective Treatment in Sideroblastic Anemia, Immunodeficiency, Periodic Fevers, and Developmental Delay (SIFD)

Colchicine

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

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