Given his clinical status, he underwent matched-related donor HCT without conditioning at 18 months of age. His respiratory status worsened and he was re-cannulated for ECMO. Due to nephrotoxicity, cidofovir was switched to brincidofovir. Trimethoprim-sulfamethoxazole, cidofovir, and immunoglobulin replacement was initiated. No other pathogenic variants in disease-causing genes were identified. The CADD PHRED score is 23.6, indicative of pathogenicity. This variant is absent in gnomAD with allele coverage of at least 183,383. Clinical whole genome sequencing (PerkinElmer®) demonstrated a hemizygous missense variant in IL2RG c.664C > A, resulting in substitution of an arginine at amino acid position 222 with serine (p.Arg222Ser). T cell receptor (TCR) spectratyping was abnormal, with 19 of 28 probes demonstrating an oligoclonal distribution and 8 with a polyclonal non-Gaussian distribution. This study was obtained while the patient was receiving systemic steroids for treatment of PJP. T cell proliferation showed low viability with impaired T cell response to phytohemagglutinin, but normal to pokeweed. TREC analysis was slightly low at 6610 copies per 10 6 T cells (ref ≥ 6794). IgG to tetanus was detectable, but IgG to Haemophilus influenzae was absent. IgG was low with near-normal IgM and normal IgA levels. The percentage of CD3+ HLA-DR+ T cells was normal for age (4.2%). CD4 +/CD45RA + naïve T cell numbers were low (Fig. Lymphocyte subsets analysis obtained 3 days after admission showed severe CD3 + T and CD16 +/CD56 + NK cell lymphopenia with elevated CD19 + B cells. Laboratory evaluation on admission revealed normal absolute lymphocyte count of 6110/μl, and elevated neutrophil count of 24,150/μl. Testing for CMV, HSV, and HHV-6 was negative. His cerebrospinal fluid and blood were both positive for adenovirus with a viral load of 664,000 copies/mcl in the blood. Cultures from BAL and blood for acid-fast bacilli and fungus were negative. Direct fluorescent antibody staining for Pneumocystis jiroveci was positive. Bronchioalveolar lavage (BAL) was positive for adenovirus and coronavirus OC43. There was no lymphadenopathy or hepatosplenomegaly. The lungs exhibited bronchial breath sounds. Upon transfer to our institution, his physical exam revealed poor growth with weight, length, and head circumference at the 7th, 3rd, and 1st percentile for age, respectively. One month after hospitalization, he continued to require ventilator support and a chest CT scan revealed patchy consolidations bilaterally (Supplemental Fig. He was treated with vancomycin, meropenem, and methylprednisolone. Chest radiographs revealed bilateral ground-glass opacities (Supplemental Fig.
#LEAKY SCID FULL#
He had one full 4-year-old sister and a paternal half-brother, both of whom were healthy. There was no family history of immunodeficiency. His immunizations were up-to-date through 6 months of age, including live rotavirus vaccines. He had a normal TREC screen at birth, 440 copies/mcl (reference ≥250). At 15 months, he was re-hospitalized for respiratory failure with adenovirus and coronavirus OC43 detected by PCR from tracheal aspirates. He was intubated for 1 month, hospitalized for a total of 6 weeks, and ultimately discharged home. A respiratory viral polymerase chain reaction (PCR) was positive for rhinovirus and adenovirus. A previously healthy 1 year old African-American male, born full term without complications, initially presented with respiratory failure requiring ECMO at an outside hospital for 9 days.
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