Homozygous C1qA Deficiency Presenting as Early-Onset Systemic Lupus Erythematosus: A Case Report With a Literature...

Childhood-onset systemic lupus erythematosus (cSLE) can be particularly severe when associated with inborn errors of immunity. Hereditary C1q deficiency is an exceptionally rare complement disorder that confers a very high risk of early, aggressive lupus. Reporting this case highlights the need to consider complement deficiencies in young children presenting with lupus-like features and recurrent infections and illustrates the diagnostic value of integrating immunologic and genetic testing.

A 3-year-old girl presented with recurrent infections, a photosensitive rash, and persistent leukopenia, raising clinical suspicion for an underlying complement deficiency in the context of cSLE. Laboratory evaluation showed strongly positive antinuclear antibody (ANA) and anti-SSA antibodies, with normal C3 and C4 levels but markedly reduced CH50. Lymphocyte subset analysis by flow cytometry was unremarkable. Western blot analysis and whole-exome sequencing identified a homozygous nonsense variant in C1qA (c.622C > T; p.Gln208 ^∗), confirming complete hereditary C1q deficiency. Despite treatment with corticosteroids and hydroxychloroquine, the patient's disease activity remained suboptimal, leading to consideration of hematopoietic stem cell transplantation as a definitive therapeutic option.

This case emphasizes the importance of early recognition and systematic evaluation of complement deficiencies in pediatric patients with lupus manifestations and recurrent infections. Identifying hereditary C1q deficiency has crucial implications for diagnosis, prognosis, and timely selection of advanced therapies, including hematopoietic stem cell transplantation, in severe forms of cSLE.