Successful Management of Delayed-Onset Adenosine Deaminase Deficiency with Novel Mutation

Abstract

A 4-year-old boy presented with acute-onset autoimmune cytopenia with severe, persistent lymphopenia, autoimmune thyroiditis, elevated IgE and glucose 6-phosphate dehydrogenase enzyme deficiency. In immunologic evaluation, lower T, B and natural killer cells and higher levels of adenosine deaminase (ADA) metabolites were observed. The compound heterozygous novel ADA gene mutations causing ADA deficiency were detected. Successful immunologic and metabolic cure was achieved with enzyme replacement therapy, followed by reduced intensity conditioning hematopoietic stem cell transplantation from a matched unrelated donor. An interesting aspect of this patient is the detection of novel compound heterozygous mutations without consanguinity and a secondary outcome is the recovery of glucose 6-phosphate dehydrogenase deficiency after hematopoietic stem cell transplantation.

Keywords::

• adenosine deaminase deficiency
• delayed onset
• enzyme replacement therapy
• hematopoietic stem cell transplantation
• late onset
• severe combined immunodeficiency

Author contributions

Conceptualization: FÇ Çelik; data curation: FÇ Çelik, Ö Soyöz, SÖ Bölük, İ Taşkırdı, İA Hacı, MŞ Kaya, A Demir, B Uzunoğlu, AT Yıldırım, H Onay, S Gözmen, N Gülez, F Genel; formal analysis: FÇ Çelik, Ö Soyöz; investigation: FÇ Çelik, AT Yıldırım, H Onay, S Gözmen, N Gülez, F Genel; methodology: FÇ Çelik, N Gülez, F Genel; supervision: FÇ Çelik, SÖ Bölük, İ Taşkırdı, İA Hacı, MŞ Kaya, A Demir, B Uzunoğlu; validation: FÇ Çelik, H Onay, S Gözmen, N Gülez, F Genel; visualization: FÇ Çelik, N Gülez, F Genel; writing – original draft: FÇ Çelik; writing – review and editing: FÇ Çelik, Ö Soyöz, H Onay, S Gözmen, N Gülez, F Genel

Acknowledgments

The authors acknowledge Michael Hershfield from Duke University School of Medicine, Department of Biochemistry, for studying ADA enzyme activity and metabolites and his valuable contribution.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent form was also received from the patient.

Data sharing statement

The data of the case report will be shared if requested.