Although sideroblastic anemias may be associated with different etiologies, general abnormality is deterioration of mitochondrial heme biosynthesis in bone marrow erythroid cells. Biallelic mutations in the TRNT1(CCA-adding transfer-RNA nucleotidyl-transferase) gene have been shown to cause a syndromic form congenital sideroblastic anemia associated with B-cell lymphopenia, hypogammaglobulinemia, growth retardation and periodic fever syndrome(SIFD).
A 7-year-old boy presented with complaints of frequent upper respiratory tract infections and bronchitis since 6-months of age.He was the second-child of consanguineous healthy parents and followed-up by Hematology Department because of anemia for 4-years.Iron deficiency,hemoglobinopathies and immune hemolytic anemias were excluded.
Physical examination findings on admission were as follows; weight and height percentiles were 10%,the liver was enlarged to 4cm and the spleen to 2cm palpabl below the costal margins. Laboratory investigations showed anemia (WBC 5590/mm3,Hb 8.2g/dl, Htc 24%,MCV 57fl,platelet 306000/mm3), anisocytosis,poikilositoz and ring sideroblasts in peripheral smear, hypogammaglobulinemia (IgG464mg/dl, IgM29mg/dl, IgA20mg/dl), negative Direct-coombs-test, normal lymhocyte subsets (CD3+67%,CD19+6%,CD3+CD4+28%,CD3+CD8+35%,CD3-CD16/56+14%) and inadequate specific-vaccine responses. Thorax CT showed nonspecific pulmonary nodules.The patient was followed-up with the preliminary diagnosis of common variable immunodeficiency and received regular intravenous-immunoglobulin replacement.A mild increase in immunoglobulin levels was observed with age.Targeted next-generation sequencing of a comprehensive IonAmpliSeqâ„¢PrimaryImmuneDeficiencyResearch Panel detected a homozygous mutation(c.914A>T,p.Asp305Val) in TRNT1 gene at the age of 14-years.
SIFD is due to loss-of-function mutations in the TRNT1 gene. Childhood TRNT1 disease/SIFD(OMIM#612907) is included in the antibody deficiencies group in IUIS Primary Immunodeficiency-2017 classification. The patient was presented to emphasize that TRNT1 disease should be considered in the differential diagnosis of anemia and hypogammaglobulinemia.