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Título

Rare homozygous mutation in complement C6 deficiency: A case report in a Brazilian child

Resumo

Introduction: The complement system is crucial in immune defense against bacterial infections and in preventing autoimmune diseases. Complete complement C6 deficiency (C6D) is a rare autosomal recessive disorder reported mainly in Afro-American populations and is characterized by recurrent infections by encapsulated bacteria. We report the case of an 8-year-old boy from northeast Brazil, born to consanguineous parents. The patient had a medical history of congenital hypothyroidism, congenital hypocortisolism, recurrent pneumonia and otitis. Immunological evaluation revealed normal levels of T and B lymphocytes, NK cells, antibodies (IgA, IgM, and IgG) and IgG subtypes. The production of antibodies to polysaccharide antigens was normal. However, hemolytic complement (CH50) activity was continuously undetectable, suggesting a complement deficiency. Further investigation via mass spectrometry test to assess inborn errors in organic acid metabolism revealed elevated levels of C5-OH (acylcarnitine), aspartic acid, 3-OH isovalerylcarnitine, and valine/phenylalanine, indicating a possible inborn error in carboxylase metabolism. Genetic analysis revealed a novel homozygous mutation in the C6 gene (c.1879del), resulting in complete C6 deficiency. A homozygous mutation in the C9 gene (c.1394C>T) was also identified, although it did not have apparent clinical consequences. Discussion: This case represents the first Brazilian child diagnosed with a pathogenic homozygous C6 mutation (p.Asp627Thrfs*4), coexisting with inborn errors in carboxylase metabolism. It underscores the importance of investigating complement deficiencies in patients with recurrent infections by encapsulated bacteria. Finally, this report expands the understanding of C6 deficiency beyond its previously recognized geographical and ethnic prevalence.