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TRNT1 DISEASE PRESENTING WITH CONGENITAL HEMOLYTIC ANEMIA AND HYPOGAMMAGLOBULINEMIA

Lecture Time
10:26 - 10:27
Presenter
  • Neslihan E. Karaca, Turkey
Room
Poster Area
Date
20.09.2019, Friday
Session Time
10:00 - 17:00
Board Number
130
Presentation Topic
Other

Abstract

Background and Aims

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).

Methods

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.

Results

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.

Conclusions

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.

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