Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review.

INTRODUCTION: Recurrent opportunistic infections are particularly common in patients infected with human immunodeficiency virus (HIV). However, these opportunistic infections have also been reported in HIV-negative patients, especially those with primary immunodeficiency disorder (PID), a condition that involves a large heterogeneous group of disorders arising from defects in immune system development and/or function.

CASE: Here, we report a very rare case of recurrent opportunistic infections in a non-HIV-infected patient combined with mutations in complement component C6 and nuclear factor kB subunit 1 (NFKB1). The patient first developed Pneumocystis jirovecii pneumonia, followed by cytomegalovirus esophagitis. Reduced CD4+ T and B lymphocyte counts, hypogammaglobulinemia were observed. The patient was HIV negative, and congenital immunodeficiency-related genes indicated combined C6 and NFKB1 mutations. Gene detection was undertaken with blood samples from the patient's parents and younger brother. None of the family members possessed both gene mutations, suggesting that the simultaneous mutations of C6 and NFKB1 caused primary immunodeficiency in the patient and resulted in recurrent opportunistic infections. In addition, we performed a review of the relevant literature to assess the clinical manifestations of C6 and NFKB1 mutations.

CONCLUSION: A diagnosis of PID should be suspected in patients with recurrent opportunistic infections, decreased CD4+ T and B lymphocyte, and hypoimmunoglobulinemia when secondary immunodeficiency factors can be excluded. In addition, genetic testing of family members should be performed, which may lead to the discovery of novel familial gene mutations.