Age: 0.17
Sex: F
Vaccine: RV5
Symptoms: Escherichia urinary tract infection, Failure to thrive, Flow cytometry, Gastrostomy, Graft versus host disease
Clinical narrative: This literature marketed report was received from authors of a published article and refers to a 2-month-old infant female patient who presented at 4 months of age via inpatient consultation to allergy/immunology, with a chief complaint of lymphocytopenia (1.01 x 10^3 cells/microL), failure to thrive, thrush, persistent diarrhea, and recurrent respiratory illnesses. She was born uneventfully via normal spontaneous vaginal delivery to nonconsanguineous parents. At 2 weeks of age, she developed oral thrush, with failure to resolve despite 5 courses of antifungal therapy. Simultaneously, she also developed bronchiolitis that never resolved, with 6 primary care visits and 3 emergency department visits for respiratory symptoms before consultation. On an unknown date, when the patient was approximately 2 months old, she received immunizations that included ROTATEQ (dose, lot # and expiration date were not provided). Later, 4 weeks after immunizations around 3 months of age, she developed persistent watery diarrhea. The physical examination at 4 months showed an ill-appearing infant with adherent white plaques in the posterior oropharynx, diffuse expiratory crackles, and an erythematous, macerated diaper rash, without hepatosplenomegaly or lymphadenopathy. Flow cytometry demonstrated total CD3+ T-cell count 30 cells/microL, CD4+ T-cell count 30 cells/mL, CD8+ T-cell count less than 10 cells/microL, natural killer (NK) cell count 949 cells/microL, and B-cell count less than 10 cells/microL. Quantitative immunoglobulins demonstrated immunoglobulin (Ig) G 66 mg/dL, IgM less than 5 mg/dL, and IgA less than 5 mg/dL. Chest x-ray was notable for an absent thymic shadow and no focal consolidations. Infectious workup was positive for rhinovirus, parainfluenza, and rotavirus by polymerase chain reaction, and oral/esophageal candidiasis confirmed by fungal culture. A diagnosis of T-B-NK+ severe combined immunodeficiency (SCID) was made based on laboratory and imaging findings, the presence of multiple infections, and failure to thrive. Targeted genetic sequencing demonstrated compound heterozygous deletions of the DCLREC1 gene, including a gross deletion of exons 1 through 8 that has not been previously described. Testing for maternal T-cells indicated an absence of maternal DNA in peripheral blood CD3+ cells. At 5 months of age, the patient had a gastrostomy tube placed for severe malnutrition. She then underwent an unconditioned, CD34+ 24.7 x 10^6/kg selected megadose haploidentical paternal donor stem cell transplant (SCT) with CD3+ dose of 2.8 x 10^4/kg at 6 months of age. The CD34+ donor selection process was conducted using a Miltenyi Biotech Inc. CliniMACS CD34+ reagent system, which uses a CD34+ monoclonal antibody conjugated to an iron-dextran moiety. The target dose of CD34+ cells was greater than 20 x 10^6 CD34+ cells/kg, which is considered a ''megadose'' of CD34+ cells, and a target T-cell dose of 3 x 10^4 CD3+ cells/kg. Approximately 60 days post-SCT, she had worsening of her known viral infections, with no evidence of donor cell engraftment. Therefore, at 8 months of age, she underwent a second unconditioned CD34+ 48.9 x 10^6/kg selected megadose stem cell boost with CD3+ dose of 1.5 x 10^4/kg. At 9 months of age, she developed Escherichia coli bacteremia. By 10 months of age, she demonstrated engraftment of paternal T-cells. Unfortunately, she also developed worsening diarrhea and a diffuse rash. Skin and gastrointestinal biopsies confirmed pathology consistent with graft-versus-host disease (GVHD). She received etanercept 0.4 mg/kg subcutaneously for 8 doses within the first month of GVHD and was started on a regimen that she continued indefinitely, including beclomethasone 1 mg by mouth every 6 hours, tacrolimus 0.4 mg by mouth every 12 hours, prednisolone 6 mg by mouth daily, alpha-1 proteinase inhibitor 60 mg/kg intravenously weekly, and as needed topical hydrocortisone 1% cream, triamcinolone 0.1% cream, and clobetasol 0.05% ointment. At 14 months of age, she had a simultaneous E coli urinary tract infection (UTI) and Staphylococcus epidermidis bacteremia. At 18 months of age, she developed respiratory distress and hypoxia secondary to infection and worsening pulmonary GVHD and died.