Selective IgM Deficiency with Combined Lymphocyte Abnormalities and Aortic Root Dilation: A Potential Novel Inborn Error of Immunity

BackgroundRecurrent bacterial pneumonia accompanied by atypical systemic findings may indicate an uncharacterized inborn error of immunity (IEI). We report a 10-year-old male with recurrent pneumonias, mildly low but functional IgM, subtle combined immunologic abnormalities, and unexplained aortic root dilation, suggesting a potentially novel immunogenetic phenotype.Case PresentationThe patient had four hospitalizations for bacterial pneumonia over the past year. His 7-year-old brother has had two pneumonias but is otherwise healthy. Parents are consanguineous, with no family history of connective tissue or immunologic disorders.Pulmonary FindingsChest CT revealed bilateral nodular and patchy opacities with early bronchiectasis. Bronchoscopy demonstrated a large amount of thick, purulent secretions, suggesting impaired airway clearance; fungal and mycobacterial studies were negative. He required inpatient airway clearance and now uses Aerobika and AffloVest at home. Sweat chloride and pancreatic elastase were normal.Immunologic EvaluationQuantitative IgG and IgA were normal; IgM was mildly low (41–47 mg/dL). Anti-blood group B isoagglutinin titer was 1:4, indicating low but detectable functional IgM. Initial pneumococcal serotype titers were low, but post-immunization responses were adequate (15/23 protective). Lymphocyte subsets showed low absolute CD8 counts, decreased memory (CD45RO+) T cells, and low natural killer (NK) cells, consistent with a subtle combined immunologic defect. Clinical whole-genome sequencing revealed no pathogenic, likely pathogenic, or variants of uncertain significance, leaving the etiology unexplained.Cardiovascular and Connective Tissue FindingsEchocardiography showed a moderately dilated aortic root (Z +4.8), dilated sinotubular junction (Z+5.4), and ascending aortic dilation. The patient demonstrates flexibility and hypermobility, though not enough to meet criteria for hypermobile Ehlers-Danlos. No features of Marfan or Loeys-Dietz syndrome were present.ConclusionThe combination of recurrent pneumonias, mildly low but functional IgM, mild T and NK cell abnormalities, early bronchiectasis, impaired airway clearance, and significant aortic dilation represents a phenotype not described in current IEI classifications or known connective tissue disorders. These findings raise suspicion for a novel or unclassified IEI with vascular involvement, highlighting the need for multidisciplinary management and research-level genomic and functional investigation.