Prognostic Factors for Sideroblastic Anemia with B-cell Immunodeficiency, Periodic Fevers, and Developmental Delay Due to TRNT1 Gene Mutations: A Case Report and Systematic Review

TL;DR

This paper reports a case of a rare genetic disorder called SIFD and identifies factors that affect patient survival, such as early onset and low B-cell counts.

Contribution

The study identifies novel TRNT1 gene mutations and provides survival probabilities based on clinical factors in SIFD patients.

Findings

Younger age of onset (≤ 3 months), seizures, and decreased B-cell count are significant poor prognostic factors for survival in SIFD.

Anti-TNF therapy may stabilize patients with autoinflammatory phenotypes, but the role of HSCT remains controversial.

Kaplan-Meier survival probabilities were estimated for different patient subgroups based on clinical features.

Abstract

Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD), a rare multisystemic syndrome, occurs due to loss-of-function mutations in the tRNA nucleotidyl transferase 1 (TRNT1) gene. This study reports the case of a 21-month-old female patient with SIFD and compound heterozygous mutations c.824T > A, p.Leu275X (a novel variant) and c.1246 A > G, p.Lys416Glu in TRNT1 gene. The patient had presented with recurrent fever since 10 days of age, along with vasculitis, systemic inflammation with elevated proinflammatory cytokines, decreased B-cell count, and failure to thrive. Furthermore, she did not respond to intravenous immunoglobulin (IVIG) treatment, but her condition stabilized with etanercept (a tumor necrosis factor [TNF] inhibitor) and corticosteroids therapy. In addition, this study includes a systematic review of the clinical presentations, genetic mutations, treatments, and outcomes of 75 patients with SIFD. The estimated 2-, 5-, and 10-year Kaplan–Meier survival probabilities for all patients were 88.45%, 76.67%, 68.84% for all patients; 82.40%, 58.86% and 44.85% for patients with onset age of ≤ 3 months; 70%, 40% and 26.68% for patients with seizures; 88.05%, 66.62% and 59.22% for patients with decreased B cell number; 50% and 33.33% for patients who received hematopoietic stem cell transplantation (HSCT), respectively (log-rank P < 0.05). We concluded that younger age of onset of ≤ 3 months, seizures, and decreased B-cell count are significant poor prognostic factors for survival. Anti-TNF therapy early in life may stabilize patients with autoinflammatory phenotypes; however, the role of HSCT remains controversial.

The online version contains supplementary material available at 10.1007/s10875-026-02000-6.

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