A 6-year-old male with a history of recurrent stomatitis was admitted for a flare associated with inability to eat. He was noted to be small for age, and the parents reported that he had a long-standing history of recurrent otitis media (with PE tube placement) and poor dentition with tooth loss. There was no history of pneumonia or infections of the skin up to this time; the umbilical cord separated around three weeks of life. Family history was notable for consanguinity (parents are first cousins). On admission, a persistent leukocytosis was noted, and symptoms improved with supportive care. Given the history of poor growth, recurrent stomatitis, and familial consanguinity, a trio exome was performed, which identified two parentally inherited ITGB2 missense variants associated with LAD type 1 (and previously reported in affected individuals in the literature).
After initiation on antimicrobial prophylaxis, his ear infections resolved and his periodontal disease had improved (but did not resolve). Immune evaluation was unremarkable, and assessment of CD18 expression in neutrophils was undertaken for risk stratification. It was assumed that this patient, given his age and manifestations, would likely have moderate risk. The first two assessments found completely normal CD18 expression (100%) with slight affectation of CD11a in the neutrophils. However, given his more concerning history, samples were sent to two other clinical laboratories. These both noted <2% CD18 expression with variable CD11a and CD11b expression, categorizing him as severe LAD1. This highlights the importance of reliable laboratory assessments in stratification of LAD1 patients.
It has been reported that this specific missense mutation allows for some co-expression of CD11b and CD11c (but not CD11a); this may explain why this patient’s clinical course had been somewhat abrogated. However, definitive therapy will likely still be needed.
HLA typing has not been successful in finding him a sibling or matched unrelated donor; given the high morbidity associated with severe LAD1 and with less-than-ideal transplants, this patient is a good candidate for gene therapy once available. In the meanwhile, antimicrobial prophylaxis and appropriate dental and ENT care are essential to keep him healthy.
