Although common CTLA4 gene variants have been implicated in the predisposition to several autoimmune conditions [3–5], it was not until 2014 that the first cases of CTLA4 deficiency (CTLA4-D) were described as a rare autosomal dominant immune dysregulation disorder caused by novel germline uniallelic mutations [6, 7]. This evidence concerns the gene CTLA4 and hyperinsulinemic hypoglycemia, familial, 4.