ESPE Abstracts

Background: Recombination-activating genes (RAG) 1 and 2 have a key role in adaptive immunity plasticity protecting against enormous diverse antigens [1]. RAG1/RAG2 defects result in several forms of primary immunodeficiencies (PI) which are, nowadays, increasingly treated by Hematopoietic Stem Cell Transplantation (HSCT) [1-3]. Both, PI and HSCT, predispose to autoimmune thyroid disease (AITD) which is otherwise uncommon in young children [4,5]. It is believed that immune reconstitution following HSCT is the likely pathogenesis for AITD. We present post-HSCT AITDs in two toddlers with Severe Combined Immunodeficiency (SCID) due to RAG1/RAG2 defect and, to our knowledge, only three similar cases have been reported in the literature [5,6].

Case Presentation:

Case 1: A 22-months-old girl who was born to consanguineous parents with family background of SCID. Since birth, she had persistent lymphopenia, significant eosinophilia and absent IgG, IgM and IgA. At 2 weeks of age, she developed chronic diarrhea, eczematous skin rash, poor feeding and recurrent viral pneumonitis. Genetic testing confirmed SCID due to homozygous RAG2 mutation at the age of 4 weeks. She underwent Haplo-HSCT (mother was the donor) following myeloablative conditioning when she was 9 months old. 13 months later, she was diagnosed with autoimmune hypothyroidism following history of severe fatigue [TSH >100 IU/L, FT4 5.4 pmol/l (9.5-17.8), anti-TPO 271 kIU/l (0-10), thyroid-receptor autoantibodies (TRAB) 28.6 IU/L (< 1.75)]. levothyroxine was started (titrated-up to 5.5 mcg/kg/day) and the patient became euthyroid in 12 weeks.

Case 2: A 3-years-4-months old girl who was part of a multiple pregnancy to consanguineous parents. She was investigated for SCID since day 2 of life because of the strong family history of PI (older brother and uncle with RAG1 mutation and the father has hypogammaglobulinemia) and initial workup showed lymphopenia with very low T cells, reduced B cells, and normal NK cells on lymphocyte subsets. The diagnosis was confirmed by detection of homozygous RAG1 gene mutation. She underwent unrelated mismatched HSCT at the age of 14 months. Two years later, she developed Graves' Disease which was confirmed by the significantly high TRAB. She had no goiter or eye signs. The patient was managed with carbimazole (titrated-up to 0.7 mg/kg/day) and became euthyroid clinically, however it was difficult to achieve biochemical euthyroidism in up to 14 weeks.

Conclusion: Young children with PI are vulnerable to develop AITDs following HSCT. Suspicion and surveillance for the condition, at least annually, is warranted.