A Unique Pathogenic Heterozygous Hyou1 Mutation Presenting with Recurrent Osteomyelitis

Several genetic mutations have been linked to recurrent infections that vary in severity from mild to life threatening. A mutation of the hyou1 gene has been associated with a defective protein resulting in poor cellular homeostasis from stress related to lack of necessary substrates for energy production, which is known to lead to a unique pattern of recurrent infections and hypoglycemia. We present a case of a 32-year-old female with chronic shortness of breath, a history of recurrent osteomyelitis, chronic sinusitis, and medically treated hypoglycemia. The patient's family history was notable for hypoglycemia in other family members. Investigative results indicated a fixed airway obstruction and a heterozygous pathogenic mutation in the hyou1 gene (exon 23, c.2638G>A), with normal immunoglobulins, lymphocyte subpopulations, and neutrophil oxidative burst assay within normal ranges. The airway obstruction was attributed to an infectious subglottic stenosis. We propose that her recurrent osteomyelitis, the infectious subglottic stenosis, and medically treated hypoglycemia are linked to her pathogenic heterozygous hyou1 mutation. Previous reports of other hyou1 homozygous mutation variants have similarly documented recurrent infections, an undefined immunodeficiency and hypoglycemic episodes. This is the first reported case of a unique pathogenic heterozygous hyou1 mutation presenting with recurrent osteomyelitis, chronic subglottal infections, and medically treated hypoglycemia.