Deficiency of adenosine deaminase 2: a recently described autoinflammatory disease with neurological manifestations (p1.254)

Objective: To characterize the neurological symptoms for Deficiency of Adenosine Deaminase Type II (DAD2), analyze the relationship between CECR1 mutation location and neurological findings, and report a case with a novel CECR1 mutation Background: DAD2 is an autoinflammatory disease caused by mutations in the CECR1 gene yielding recurrent fever, livedo reticularis, and neurological symptoms. We analyzed published cases of DAD2 to provide broader characterization of the neurological manifestations of this disorder. We also report a 6-year-old boy who presented repeatedly over several years with a constellation of findings from DAD2. Design/Methods: A literature search yielded 117 DAD2 cases, 90 had sufficient clinical details for analysis. Characteristics such as age, clinical symptoms, imaging findings, labs, and treatments were recorded. The relationship between CECR1 mutation location and neurological symptoms was analyzed. Statistical analysis including chi-square and logistic regression were performed in SAS. Results: 91 cases were analyzed, 51 male. Median age at neurological symptom presentation was 3 years and ranged from one month to 42 years. Neurological symptoms were found in 59%(54), and categorized as ocular dysfunction(32), appendicular motor or sensory dysfunction(25), coordination disturbances(16), speech difficulty(12), altered mental status(12), headache(10), developmental delay(4), seizure(3), or other(15). MRI findings of an infarction, hemorrhage, or other abnormality were found in 52%(28), 19%(10), and 15%(8) respectively. Lacunar lesions were seen in 44%(24). Hypogammaglobulinemia, elevated inflammatory markers and abnormal immunological labs were most often associated with neurological symptoms but not statistically significant. Neurological symptoms or MRI infarction/hemorrhage were significantly associated with mutations between amino acids 154–204 (OR 3.6, CI 1.097–11.685). Conclusions: DAD2 involves a spectrum of neurological symptoms and MRI findings. Mutations at amino acids 154–204 of the CECR1 gene are more likely to cause neurological symptoms than mutations elsewhere in CECR1. A better understanding of these neurological manifestations will aid in earlier diagnosis, which can reduce morbidity, mortality, and unnecessary testing. Disclosure: Dr. Noll has nothing to disclose. Dr. Kessler has nothing to disclose. Dr. Gratton has nothing to disclose.