Pathogenic variants in the protein kinase C delta (PRKCD) gene cause autoimmunity, humoral immunodeficiency and recurrent infections. Previously described patients showed B-cell lymphopenia with normal T-cell numbers, dysgammaglobulinemia and impaired class-switching without notable pulmonary manifestations.
Chart review and clinical care of patient.
A Palestinian male with consanguineous parents presented at 15 months with joint swelling, splenomegaly, rash and fevers. Elevated inflammatory markers and positive ANA, anti-phospholipid, anti-Smith, and anti-double stranded DNA antibodies were noted. At 6 years, he developed immune-mediated cytopenias (positive DAT and anti-neutrophil antibodies). CD3, CD4 and CD8 absolute values were decreased; T-cell proliferation to antigens was reduced. CD19 absolute value was normal; IgG and IgM were low. Alpha/beta CD3+CD4-CD8- T-cells were 13.7% but pathogenic variants in FAS were not identified. Mycophenolate improved his lymphoproliferation and cytopenias. His course was complicated by frequent fungal/bacterial infections (sinusitis, orbital cellulitis and pneumonias) resulting in bronchiectasis and chronic atelectasis requiring azithromycin treatment and daily chest physiotherapy. At 18 years he was referred for further immunologic evaluation with genetic testing revealing a novel homozygous PRKCD variant (c.1872+1G>A). Reduced class-switch (CD19+CD27+IgD-) and total memory B-cells were noted. IVIG replacement was initiated.
Our patient expands the clinical, immunologic and genetic phenotype of PRKCD deficiency by showing prominent pulmonary manifestations, displaying quantitative & qualitative T-cell deficits in-addition to B-cell abnormalities, and harboring a novel pathogenic variant. Undefined immunologic dysregulation patients should be regularly assessed for newly discovered genetic alterations given the ever-changing genetic landscape of immunodeficiency conditions.