We report a 5 year old boy initially evaluated for acute temporary vision disorder – blurred vision and diplopia, afebrile. MRI scan showed oval lesion 6x7x7mm in parasagittal mesencephalic region, slightly increased signal in T2W, with restricted diffusion in DWI, no signs of hemorrhage. Clinical immunologist consultation was requested for suspicion of autoimmune encephalomyelitis. Hypogammaglobulinemia IgG, IgA, IgM with low B cells and low post-vaccination antibodies have been detected. Patient was classified under CVID follow-up group and placed on regular IG replacement. Within next months he remained asymptomatic, with low inflammatory markers.
Targeted NGS for genes associated with PID was performed on MiSeq (Illumina) in the patient. Mutations were confirmed by Sanger sequencing.
NGS analysis revealed 2 missense variants in ADA2 gene in trans configuration. 1) c.506G>A (p.R169Q) was previously described as disease causing mutation, in association with antibody deficiency and inconstantly with vascular manifestation; 2) c.505C>T (p.R169W) novel variant was revealed in a neighboring DNA position, affecting the same amino acid; prediction tools evaluated it as damaging and a change of the same amino acid has already been described as disease causing mutation, indicating that this variant can be considered pathogenic as well.
We describe a patient carrying compound heterozygous loss-of-function mutations in ADA2 gene presenting under an overlapping phenotype of unspecific focal neurologic symptomatology associated with an ischemic stroke and immunodeficiency of B cell compartment. NGS methods are the best choice for detecting molecular defects in preschool age hypogammaglobulinemia patients.