TPP2

Clinical Characteristics

Two different phenotypes are associated with biallelic pathogenic variants in TPP2:

•    A childhood onset multisystemic severe phenotype: described to date in 10 patients presenting with recurrent upper and lower tract respiratory infections, autoimmune cytopenias, developmental delay of variable degree and progressive combined immunodeficiency predisposing patients to severe viral infections (CMV, VZV, HSV, HPV15). They may develop a broad range of non-specific autoimmune diseases including autoimmune hepatitis, atopic dermatitis, Hashimoto thyroiditis, diffuse alopecia, cutaneous vasculitis, ileitis and probably cerebral vasculitis which may induce strokes.


•    Late-onset adult phenotype: described in four patients with chronic non-infectious brain inflammation with demyelinating disease and calcifications mimicking multiple sclerosis. Recurrent upper respiratory tract infections and mild lymphopenia seems to be also common features in those patients. Psoriasis was described in two patients.