D2.381 - Early Infantile Immune Dysregulation with an Atopic Phenotype: A Case of Genetically Confirmed Otulipenia
Case report
Introduction: Loss of function in the OTULIN gene disrupts linear ubiquitin regulation, uncontrollably increasing NF-κB activation and leading to a rare condition called otulipenia, characterized by systemic inflammation, skin manifestations, and immune dysregulation, beginning in the neonatal/early infantile period.
Case: A female patient, born spontaneously at term weighing 3360 grams to a G3P1A1Y1 mother, whose parents are cousins, has a surviving sibling diagnosed with biotinidase deficiency. The patient presented to our emergency department at 6 weeks with severe cough and vomiting, and was admitted to the intensive care unit with a diagnosis of pneumonia. Despite broad-spectrum antibiotics and non-invasive mechanical ventilation support, her symptoms did not improve. Immunological investigations revealed oral thrush, widespread eczematous dermatitis throughout the body, hepatomegaly, and inadequate weight gain on physical examination. Laboratory tests revealed elevated IgE (2460 IU/mL), eosinophilic leukocytosis (Eo: 6–17%; absolute 0.9–2.2 x10³/µL), and elevated ferritin (1102 ng/mL). Detailed lymphocyte subgroup analysis and IgG, IgA, and IgM values were normal; no growth was observed in blood, urine, and respiratory tract cultures. Given the patient's refractory pneumonia, consanguineous marriage, history of abortion, widespread eczematous dermatitis, eosinophilia, and elevated IgE, a preliminary diagnosis of immunodeficiency with an atopic phenotype was made, and whole-exome sequencing was performed. The OTULIN (NM_138348.6): C.244G>A (p. Val82lle) rs555528904 variant was detected in homozygous form. Genetic confirmation via Sanger sequencing and single-gene point mutation analysis revealed a homozygous mutation in the OTULIN gene in the patient, and the current findings support the diagnosis of autosomal recessive otulipenia.
Conclusion: This case highlights the need to consider otulipenia in the differential diagnosis of severe infections, elevated IgE levels, and eosinophilia in early infancy, and emphasizes the critical role of genetic confirmation in the diagnostic process.
