Mutations in the regulator of telomere elongation helicase 1 (RTEL1) gene cause excessive telomere shortening, leading to bone marrow failure, dyskeratosis congenita, pulmonary and liver fibrosis, and, in some severe cases, immunodeficiency. Most severe cases of RTEL1 deficiency leading to immunodeficiency are due to biallelic mutations; however, we present a 4-month-old male with a heterozygous RTEL1 mutation who presented with hypogammaglobulinemia and recurrent tracheitis.
A 4-month-old male born at 37 weeks gestation with SCL2A and LMNA mutations, GLUT1 deficiency, seizure disorder, gastrojejunal and tracheostomy tube dependence, presented with recurrent tracheitis due to Klebsiella pneumoniae and Enterococcus faecalis. He had no history of otitis media, pneumonia, sinusitis, bacteremia, or urinary tract infections. However, at the initial consultation, all immunoglobulin levels were undetectable with normal lymphocyte subsets. Due to recurrent tracheitis and persistent hypogammaglobulinemia after 6 months of age, he was treated with monthly intravenous immunoglobulin replacement with an appropriate increase in IgG immunoglobulin levels and decreased frequency of infections. Eventually, a primary immunodeficiency genetic panel was completed and revealed two heterozygous variants of unknown significance in GUCY2C (c. 1735T>C, p.Tyr579His) and RTEL1 (c.2957G>A, p.Arg986Gln) genes, the latter of which has been associated with both cellular and humoral immunodeficiency in patients with homozygous mutations.
This case highlights the possibility of severe immunodeficiency in patients with a heterozygous RTEL1 mutation and the need for long-term immunological monitoring in these patients. Although an RTEL1 mutation has not been described as pathogenic for immune dysfunction, this patient’s clinical presentation, consisting of persistent hypogammaglobulinemia and recurrent infections, suggests that heterozygous mutations in RTEL1 should be considered as clinically significant when evaluating patients with immunodeficiency.
