A five-year-old boy presented to the emergency room (ER) with a 6-day history of fever, rhinorrhea, worsening cough, emesis, back and abdominal pain, decreased appetite, and headache. In the ER, he was found to have a temperature of 38.5  C-39.5  C, a respiratory rate of 60 breaths per minute, a heart rate of 140 beats per minute (bpm), blood pressure of 108/65, and an oxygen saturation of 96%-98% on 1/2 lpm of O2. He was tachypneic, with audible grunting, suprasternal retractions, a clear chest, mild tenderness at right upper and lower abdominal quadrants, but no guarding or rebound tenderness or hepatosplenomegaly, and no rashes. Laboratory values included a white blood cell count of 20 x 109/L, hemoglobin count of 122 g/L, platelet count of 462 x 09/L, absolute neutrophil count of 17 x 109/L, absolute lymphocyte count of 1.26 x 109/L, normal chemistry, elevated glucose of 9 mmol/L, urinalysis with glucose > 55 mmol/L and ketones. A chest X-ray (CXR) revealed right middle lobe pneumonia (Fig. 1). He was admitted to hospital and treated with intravenous ceftriaxone (75 mg/kg/day for 9 days), azithromycin (5 mg/kg/day po for 5 days) and vancomycin (20 mg/kg/day for 9 days, adjusted to a trough of 15-20).
Twenty-four hours later, due to persistent respiratory distress and increased chest pain, a repeat CXR was done and revealed extensive parenchymal involvement, mediastinal shift and a large effusion (Fig. 2). Ultrasounds of the chest and abdomen confirmed the pleural effusion, and revealed mild splenomegaly. In contrast to the degree of effusion, this child exhibited initially only moderate distress and did not appear toxic. A chest tube was inserted because of progressively worsening distress, and straw-colored pus was drained. The fluid was sent for cell count (white blood cell (WBC) 315, neutrophils 57%, platelet 7.5% red blood cell (RBC) 1210), protein (26), albumin (16), lactate dehydrogenase (LDH; 1308), lipase (17), amylase (32), gram stain (negative), culture (negative), streptococcal pneumonia polymerase chain reaction (PCR; negative), fungal culture (negative), mycobacterial culture (negative), viral culture (negative), and TB culture (negative). Blood drawn at the same time revealed a lipase of 16, amylase of 23, LDH of 168, and protein of 54. Other tests included a negative throat culture, a negative stool viral culture, negative blood culture, negative nasopharyngeal aspirate for respiratory viruses, antistreptolysin O titer (ASOT) of 134, antideoxyri-bonuclease-B (DNase B) titer < 50, and EBV titers suggestive of past infection. Nasopharyngeal aspirate was positive for mycoplasma pneumonia by PCR. There was a gradual improvement in his respiratory status during the following week and he was discharged after 9 days on amoxicillin-clavulanate (45 mg/kg BID for 7 days), followed by amoxicillin prophylaxis (250 mg po BID).
Past medical history was significant for recurrent skin and respiratory infections, including a left elbow abscess requiring drainage and oral antibiotic treatment (at the age of 5 months), pneumococcal bacteremia presenting with fever and emesis (at the age of 7 months), a retropharyngeal abscess (at the age of 9 months), and pneumonia (at the age of 3 years). Developmental history was unremarkable, and current weight was 17 kilograms (>15th percentile).
The parents are second cousins of Moroccan origin, and there is a healthy older brother.
Given the history of recurrent severe infections, he was initially evaluated at the age of 3 years by the immunology service at the Montreal Children's Hospital. His immune evaluation revealed a normal complete blood count (CBC), normal lymphocyte subsets, normal T cell proliferation to mitogens, normal serum IgG/A/M/E levels, and protective post-vaccination antibody titers to tetanus, diphtheria, hemophilus influenza, and streptococcus pneumonia. A dihydrorhodamine (DHR) test for phagocytic function was normal. Complement studies including CH50, AH50, C3, and C4 levels were normal, but there was absent activity through the mannose binding lectin (MBL) pathway for complement activation. With reproducible absence of functional MBL activity, DNA was sent for genetic analysis to identify known mutations associated with MBL deficiency. Results demonstrated a compound heterozygosity for two haplotypes in the MBL2 gene in this child. Both haplotypes identified, LYPB and LYQC, are associated with very low mannose binding protein levels. An additional polymorphism in the MBL promoter was also identified.
Given the history of significant infections associated with genetic and functional diagnosis of MBL deficiency, recommendations for management included antibiotic chemoprophylaxis, optimization of protection through routine vaccination, prompt investigation and treatment of infections, and regular immunology clinic visits to reduce the risk of long-term complications. At the time of his current admission to hospital the child was taking no regular medication, and despite repeated attempts of the immunology service to contact the family, he had been lost to follow-up. As a result, the family was not fully aware of the implications of his immunodeficiency and did not relay his underlying diagnosis to the ER staff.