A case report of a pediatric patient with coexisting Bruton agammaglobulinemia and Wilson disease (WD) caused by new mutations in the ATP7B and BTK genes has been recently published in Allergologia et Immunopathologia.

Due to their low prevalence and incidence, WD and Bruton agammaglobulinemia are regarded as rare diseases. The former has an autosomal recessive inheritance pattern characterized by a mutation in the ATP7B gene, and the latter is an X-linked recessive hereditary disease caused by a mutation or deletion in the BTK gene. There are currently no reports of both entities coexisting in the same patient. 

Read more about Wilson disease epidemiology

The ATP7B mutation in WD leads to alteration in copper metabolism, which in turn leads to varied clinical manifestations ranging from liver failure to psychiatric alterations, Bruton agammaglobulinemia, on the other hand, is a primary immunodeficiency characterized by recurrent infections and undetectable B cell levels.

“Based on their prevalence, a probability of coexistence of both entities in 1 per 18,950,000,000 inhabitants is accounted for, which indicates that it is an infrequent condition,” the authors wrote. 

The case involved a 14-year-old male without any significant family antecedents or complications at birth. Recurrent infections started during the first month after birth, including severe gastrointestinal and respiratory infections and several bouts of septic arthritis. 

Laboratory findings during this stage revealed severe hypogammaglobulinemia, and the patient was initially handled with intravenous immunoglobulin, which improved his clinical condition. At 9 years of age, he underwent genetic sequencing. The latter led to the diagnosis of Bruton agammaglobulinemia. The deletion mutation of exons 13 to 17 in the BTK found in the patients was previously unreported. 

Due to persistently elevated transaminases at age 9, the patient was referred to hepatology. The detection of low ceruloplasmin levels, low serum copper, elevated urinary cooper, and 60% micro-steatosis raised suspicion for WD.

Therapy with high-dose zinc leads to an improvement in liver function tests. Subsequent genetic sequencing showed a new mutation in the ATP7B gene, confirming the WD diagnosis. The patient is currently receiving treatment with intravenous immunoglobulin as well as high-dose zinc with satisfactory clinical progression. 

“It establishes that a patient with an established diagnosis may present a different entity and that not all clinical manifestations are attributable to the underlying disease,” the authors wrote. 


Olaya M, Aristizabal C, Perez Camacho P, et al. First Report of Wilson disease and Bruton Agammaglobulinemia  in the same patient caused by new mutations in ATP7B and BTK genes. Allergol Immunopathol. Available online May 1, 2023. doi:10.15586/aei.v51i3.770