XLA characterized by increased susceptibility to severe hypogammaglobulinemia-related infections. Heterozygous females carry a mutant allele on one X chromosome, leading to variable expression of the disorder known as mosaic pattern. Incidence of females with complete manifestations is unusual, with no reported.
A 17-year-old female diagnosed with XLA, epilepsy, and neurodevelopmental delay. WES revealed a heterozygous mutation in the BTK gene. The karyotype was 45XX, ruling out structural rearrangements on the X chromosome. She presented with edema, erythema, and functional limitation of the left ankle, managed as outpatient for cellulitis. Despite 15 days of cefalotin treatment, pain and fever persisted. Admitted and osteomyelitis was ruled out. Uncontrolled seizure activity was observed. IVIG dose was increased from 400 to 1000 mg/kg/dose. PCR on a skin biopsy was positive for Helicobacter cinaedi. Managed with meropenem and doxycycline for 6 weeks, and complete resolution of cellulitis was achieved.
BTK mutations lead to defects in B cell development, resulting in antibody production impairment and susceptibility to severe or recurrent infections. Increased susceptibility to unusual microorganisms such as non-Pylori Helicobacter species causing skin infections has been described. In patients with agammaglobulinemia and cellulitis who do not respond adequately to antibiotics, the possibility of these pathogens should be considered early on to request specific tests for diagnosis. This is crucial, as these infections require prolonged and aggressive antibiotic treatment to improve prognosis. In our patient, we suspect that the active X chromosome in most heterozygous female cells carries the mutant allele (skewed X inactivation), leading to disorder expression.
Agammaglobulinemia should be suspected in males or females with recurrent infections and hypogammaglobulinemia. Some females may exhibit clinical symptoms due to defects in BTK. In XLA patients with cellulitis, a high clinical suspicion of atypical germs like non-pylori Helicobacter should be maintained, despite adequate treatment with replacement immunoglobulin.
