Adenosine deaminase deficiency accounts for approximately 20% to 25% of cases of autosomal recessive severe combined immunodeficiency. In the majority of patients, the onset of clinical disease occurs within 1 to 6 months of age, with failure to thrive, diarrhea, persistent oral and perianal candidiasis, and recurrent viral, bacterial, and. other opportunistic infections. In 10%-15% of patients, the onset of disease may occur later than 6 months. Rarely, patients with clinical onset of disease after the second year of life have been recognized.

9-year-old was admitted with recurrent encephalitis following upper respiratory tract infections. He was born to nonconsanguineous healthy parents and was very well until the age of 6.5 years. He had fever and focal onset tonic-clonic convulsions and was hospitalized at the intensive care unit with the diagnosis of encephalitis at that time. Cranial MRI and CSF examination were found to be normal. Since then, he had 3 similar, milder  encephalitis attacks responding to supportive therapy. WES analysis showed a compound heterozygous mutation in ADA gene. 

The patient was referred to our clinic to be investigated for primary immunodeficiency diseases as he began to have frequent infections. Immunologic work-up (lymphocyte and neutrophil counts, Ig levels, lymphocyte subsets) were normal for age. In order to exclude the functional effects of the identified mutation, toxic metabolites were checked on a dried blood sample and they were found high. With the diagnosis of late-onset ADA deficiency, elapegademase-lvl was started twice a week and regular IVIG therapy. He had just once an infectious episode during the 1 year follow-up period. Toxic metabolite levels decreased.

ADA deficiency should be kept in mind in the differential diagnosis of patients presenting with recurrent infections and neurologic findings. Regular monitoring of toxic metabolite levels of patients treated wth enzyme replacement is mandatory.