We are reporting a 14-year-old male who presented at 12 years of age with recurrent episodes of hypothermia and bradycardia (30s) secondary to culture-negative septic shock from presumed viral respiratory illnesses. His temperatures on presentation are frequently below the level of detection rectally, with the lowest recorded temperature of 95.2F. Infectious testing during these episodes has only ever been positive for common respiratory viruses, including rhino/enterovirus and SARS-CoV-2. His episodes of hypothermia and shock have responded to supportive care, including warming and vasopressors. He has had 7 admissions in the past two years, with a duration of stay ranging from 4 to 23 days. There has been no decrease in length or frequency of admissions.
He has also been found to have intermittent interstitial nodular lung disease on chest x-ray. A recent chest CT is normal. He has a kidney injury that has evolved into a nephrotic syndrome. No lymphedema.
He has had persistent lymphopenia with intermittent pancytopenia. His lymphocyte subset numbers are low with an absolute CD4 count of 105 cells/μL, CD3A of 422 cells/μL, and absolute natural killer (NK) cells of 64 cells/μL. GM-CSF plasma <15.0 pg/mL during an acute episode. A bone marrow biopsy was performed, which only revealed hypocellularity.
Concomitant problems include fetal alcohol syndrome and developmental delay. He has an intronic GATA2 c.1017+572C>T heterozygous mutation. He is on prophylaxis with atovaquone, voriconazole, and azithromycin and has received HPV vaccination. He was assessed for a stem cell transplant but was not considered a candidate.
This patient’s GATA2 mutation is a single-nucleotide substitution located within intron 5 within the +9.5-enhancer element. Quantitatively, this may result in 50% reduction in GATA2 transcript levels. Not much is known about this mutation in these patients. His phenotype is different from other mutations in this gene because of recurrent hypothermia and shock. These episodes seem mostly linked with respiratory viral infections. There has been no reduction in frequency of these episodes, and now he is on homebound education.
