Research Day

The Immune Function Of A Patient With Itch E3 Ubiquitin Ligase Deficiency

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BACKGROUND: ITCH E3 ubiquitin ligase deficiency is a rare defect associated with multi-system autoimmune conditions. Previous literature has presented the symptomatology, histopathology, and genetics of select Old Order Amish patients with this condition. We present the third report of ITCH E3 ubiquitin ligase deficiency in humans and the first to include laboratory evaluation of the patient's immune function.

CASE PRESENTATION: SS is a 28-month-old unvaccinated Amish female with homozygous ITCH E3 ubiquitin ligase deficiency. She was born to consanguineous parents. A sister died from liver failure at 2 months of age. SS presented with failure to thrive, chronic diarrhea, and chronic lung disease with recurrent viral exacerbations. She developed recurrent pneumonia, recurrent skin/soft tissue abscesses, and oral candidiasis triggering further immune evaluation. Lab results showed normal quantitative immunoglobulins, absent antibody titers to tetanus, diphtheria, and S. pneumoniae, and low titer elevated ANA. She had neutropenia and normocytic anemia during times of illness. During one illness she had moderately reduced T-cell count. Due to difficult venous access, this could not be re-assessed and not all evaluations were able to be completed. The patient ultimately succumbed to respiratory failure from repeated viral pneumonitis.

DISCUSSION: This patient's presentation is in line with previous literature, but we have delineated a more detailed evaluation of the immune system. ITCH E3 ubiquitin ligase is important in promoting Treg differentiation and T cell anergy, and deficiency affects multiple cell signaling pathways and causes lethal autoimmune inflammation in multiple organs.

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