Delayed diagnosis of X-linked agammaglobulinaemia in a boy with recurrent meningitis

Abstract

BackgroundX-linked agammaglobulinaemia (XLA) is a rare inherited primary immunodeficiency disease characterized by the B cell developmental defect, caused by mutations in the gene coding for Bruton’s tyrosine kinase (BTK), which may cause serious recurrent infections. The diagnosis of XLA is sometimes challenging because a few number of patients have higher levels of serum immunoglobulins than expected. In this study, we reported an atypical case with recurrent meningitis, delayed diagnosis with XLA by genetic analysis at the second episode of meningitis at the age of 8 years.Case reportAn 8-year-old Chinese boy presented with fever, dizziness and recurrent vomiting for 3 days. The cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) results were suggestive of bacterial meningoencephalitis, despite the negative gram staining and cultures of the CSF. The patient was treated with broad-spectrum antibiotics and responded well to the treatment. He had history of another episode of acute pneumococci meningitis 4 years before. The respective level of Immunoglobulin G (IgG), Immunoglobulin A (IgA) and Immunoglobulin M (IgM) was 4.85 g/L, 0.93 g/L and 0.1 g/L at 1st episode, whereas 1.9 g/L, 0.27 g/L and 0 g/L at second episode. The B lymphocytes were 0.21 and 0.06% of peripheral blood lymphocytes at first and second episode respectively. Sequencing of the BTK coding regions showed that the patient had a point mutation in the intron 14, hemizyous c.1349 + 5G > A, while his mother had a heterozygous mutation. It was a splice site mutation predicted to lead to exon skipping and cause a truncated BTK protein.ConclusionImmunity function should be routinely checked in patients with severe intracranial bacterial infection. Absence of B cells even with normal level of serum immunoglobulin suggests the possibility of XLA, although this happens only in rare instances. Mutational analysis of BTK gene is crucial for accurate diagnosis to atypical patients with XLA.

Whole genome sequencing identifies novel structural variant in a large Indian family affected with X-linked agammaglobulinemia

“…Autoimmunity and autoinflammation can occur in XLA, and arthritis could be either due to a dysfunctional immune system or due to infection with mycoplasma, which was not the case in our patient P5 [ 30 ]. The challenge lies in identifying the index case [ 31 ]. Although panhypogammaglobulinemia is the rule, there are reports of normal immunoglobulin levels or selective immunoglobulin deficiency [ 32 , 33 ].…”

Whole Genome Sequencing identifies novel structural variant in a large Indian family affected with X - linked agammaglobulinemia

“…Autoimmunity and autoinflammation can occur in XLA, and arthritis could be either due to a dysfunctional immune system or due to infection with mycoplasma, which was not the case in our patient P5, [28] . The challenge lies in identifying the index case [29] . Although panhypogammaglobulinemia is the rule, there are reports of normal immunoglobulin levels or selective immunoglobulin deficiency [30,31] .…”