A 15-month-old boy is brought to the emergency department due to irritability and vomiting. His parents say that the patient was more tired than usual yesterday and went to bed early. This morning, he awoke crying and has been inconsolable. His mother attempted to feed him, but he has vomited twice today. Three weeks ago, the patient had similar symptoms and was admitted to the hospital and diagnosed with enteroviral meningitis. He has a history of 2 episodes of pneumonia requiring hospitalization as an infant. Temperature is 40.1 C (104.2 F). On examination, the patient is awake but crying and inconsolable in his mother's arms. Heart and lung examinations are unremarkable, and the abdomen is soft. There is a diffuse macular rash over the trunk. Lumbar puncture results are as follows:
| Cerebral spinal fluid | |
| Glucose | 50 mg/dL |
| Protein | 80 mg/dL |
| Leukocytes | 300 cells/µL |
| Red blood cells | 5 cells/µL |
Gram stain reveals no organisms. The patient is suspected to have chronic viral meningitis. Which of the following additional findings is most likely to be found in this patient?
X-linked agammaglobulinemia | |
Pathophysiology |
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Clinical manifestations |
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Laboratory findings |
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Treatment |
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This patient has chronic enteroviral meningitis and recurrent pneumonia, which are features of X-linked agammaglobulinemia (XLA). XLA (ie, Bruton agammaglobulinemia) is an immunodeficiency characterized by failure of B-cell maturation in the bone marrow due to defective Bruton tyrosine kinase signaling. B lymphocytes cannot enter circulation, resulting in decreased antibody production and impaired humoral immunity.
XLA causes recurrent infections in boys during late infancy once maternally derived IgG wanes (age >3-6 months). Sinopulmonary infections are most common and are typically caused by encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae type b), which require antibody opsonization for clearance. Patients are also predisposed to chronic enteroviral infection (eg, meningoencephalitis), as seen in this patient, due to lack of antibodies to neutralize disease. Similarly, prolonged diarrheal illness (eg, Giardia) due to low IgA is more likely in patients with XLA.
Laboratory findings of XLA include low CD19+ B-cell concentrations and decreased levels of all immunoglobulins. Antibody response to vaccines is also impaired. Immunoglobulin replacement therapy is the mainstay of treatment.
(Choice A) Intracellular killing of mycobacteria is activated by interaction of interferon gamma (IFN-γ), which is released by T cells and NK cells, and IFN-γ receptors on macrophages. IFN-γ receptor deficiency results in disseminated mycobacterial disease beginning in infancy.
(Choice C) Chronic granulomatous disease due to impaired neutrophil oxidative burst presents with recurrent skin and pulmonary infections with catalase-positive organisms (eg, Staphylococcus aureus, Serratia marcescens). Enteroviral infections are not associated with this condition.
(Choice D) Selective IgA deficiency, which is most commonly asymptomatic, can be associated with chronic diarrhea (eg, Giardia infection) but would not be responsible for enteroviral meningitis.
(Choice E) Cyclic neutropenia is characterized by recurrent episodes of reduced peripheral neutrophils, fever, sore throat, and lymphadenopathy, commonly occurring every 3 weeks. Chronic enteroviral infection is not associated with cyclic neutropenia.
Educational objective:
X-linked agammaglobulinemia is an immunodeficiency characterized by impaired B-cell maturation and antibody production. Commonly associated conditions include recurrent sinopulmonary infections, chronic enteroviral meningoencephalitis, and prolonged diarrheal illness.