D1.353 - A Rare Cause of Recurrent Infections: SIFD Syndrome

A Rare Cause of Recurrent Infectıons: SIFD Syndrome

Introduction: SIFD (Sideroblastic Anemia, Immunodeficiency, Periodic Fever, and Developmental Delay) syndrome is an autosomal recessive disorder caused by mutations in the TRNT1 gene, characterized by immunodeficiency, recurrent fever, developmental delay, and sideroblastic anemia. In this case report, we aimed to highlight the clinical features of a patient diagnosed with SIFD syndrome who presented with recurrent infections and periodic fever episodes.

Case: A four-year-old girl was admitted to our outpatient clinic with recurrent infections and repeated fever episodes. She had been diagnosed with sideroblastic anemia at two months of age and was followed by pediatric neurology due to hypotonia and motor developmental delay recognized at one year of age. She had sensorineural hearing loss in the left ear and retinitis pigmentosa on ophthalmologic examination. Brain MRI revealed hypomyelination in the subcortical and deep white matter and thinning of the corpus callosum. Metabolic disorders and leukodystrophy had been excluded. Immunological evaluation demonstrated B-cell lymphopenia, with persistently low CD19 levels during follow-up. Although the frequency of fever episodes decreased after intravenous immunoglobulin therapy, they did not completely resolve. Due to cyclic fever attacks accompanied by vomiting and diarrhea, whole-exome sequencing was performed for suspected autoinflammatory disease and revealed a heterozygous TRNT1 mutation (c.374T>G; p.Leu125Arg), leading to the diagnosis of SIFD syndrome. Etanercept and infliximab (anti-TNF) therapies were initiated; however, anaphylaxis occurred after the first dose of infliximab, and inadequate response to etanercept led to a switch to adalimumab (anti-TNF) and methotrexate.

Discussion: SIFD is a rare autoinflammatory syndrome with severe multisystem involvement, including hematologic, immunologic, neurologic, ophthalmologic, and gastrointestinal manifestations, and it often results in death within the first decade of life. To date, approximately 60 patients with TRNT1 variants have been reported. Hematopoietic stem cell transplantation is the only effective treatment option described. In patients presenting with recurrent infections, particularly when accompanied by neurological delay, hearing loss, and anemia, SIFD syndrome should be considered in the differential diagnosis.