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Neurologic Status of Patients with Purine Nucleoside Phosphorylase Deficiency Before and After Hematopoetic Stem Cell Transplantation

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Abstract

Background

Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive combined immunodeficiency. The phenotype is profound T cell deficiency with variable B and NK cell functions and results in recurrent and persistent infections that typically begin in the first year of life. Neurologic findings occur in approximately two-thirds of patients. The mechanism of neurologic abnormalities is unclear. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for PNP deficiency.

Methods

We report here six patients from five unrelated families with PNP deficiency treated in two centers in Turkey. We evaluated the neurological status of patients and compared to post-transplantation period if available. Then, we performed PubMed, Google Scholar, and Researchgate searches using the terms “PNP” and “hematopoietic stem cell transplantation” to find all reported cases of PNP transplantation and compared to our cohort.

Results

Six patients were treated in two centers in Turkey. One patient died from post-transplant complications. The other four patients underwent successful HSCT with good immune reconstitution after transplantation (follow-up 21–48 months) and good neurological outcomes. The other patient with a new mutation is still waiting for a matching HLA donor.

Discussion

In PNP deficiency, clinical manifestations are variable, and this disease should be considered in the presence of many different clinical findings. Despite the comorbidities that occurred before transplantation, HSCT currently appears to be the only treatment option for this disease. HSCT not only cures immunologic disorders, but probably also improves or at least stabilizes the neurologic status of patients.

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Data Availability

All data underlying the results are available as part of the article and no additional source data are required.

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Funding

This work was supported by the Research Fund of Istanbul University-Cerrahpasa (Project number: TOA-2021–35251).

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Authors and Affiliations

  1. Department of Pediatric Immunology and Allergy, School of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey

    Betul Gemici Karaaslan, Sezin Aydemir, Zeynep Akyuncu Meric, Ayca Kiykim & Haluk Cokugras

  2. Department of Pediatric Immunology and Allergy, University of Health Sciences, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey

    Isilay Turan, Funda Cipe & Cigdem Aydogmus

  3. Department of Pediatric Hematology/Oncology, Bone Marrow Transplantation Unit, School of Medicine, Altunizade Hospital, Acibadem University, Istanbul, Turkey

    Didem Atay, Arzu Akcay & Gulyuz Ozturk

  4. Department of Pediatric Neurology, School of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey

    Aysun Ayaz Sari

  5. Department of Medicine, Department of Biochemistry, Duke University School of Medicine, Durham, NC, Duke University School of Medicine, Durham, NC, USA

    Michael Hershfield

  6. Department of Pediatric Allergy-Immunology & Pediatric Bone Marrow Transplantation Unit Altınbas University, Medical Park Bahcelievler Hospital, Istanbul, Turkey

    Funda Cipe, Basak Adakli Aksoy & Gizem Zengin Ersoy

  7. Department of Pediatric Allergy-Immunology & Pediatric Bone Marrow Transplantation Unit Istinye University, Medical Park Bahcelievler Hospital, Istanbul, Turkey

    Ceyhun Bozkurt

  8. Umraniye Training and Research Hospital, Pediatric Genetic, Istanbul, Turkey

    Yasemin Kendir Demirkol

Authors
  1. Betul Gemici Karaaslan
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Contributions

All authors contributed to the study conception and design. Betul Gemici Karaaslan, Isilay Turan, Sezin Aydemir, Zeynep Meric, Didem Atay, Arzu Akcay, Aysun Ayaz Sari, Yasemin Kendir Demirkol, Michael Hershfield, Funda Cipe, Basak Adakli Aksoy, Gizem Zengin Ersoy, Ceyhun Bozkurt, Gulyuz Ozturk, Cigdem Aydogmus, Ayca Kiykim, and Haluk Cokugras followed patients, collected samples and provided clinical data. Material preparation, and data analysis were performed by Betul Gemici Karaaslan, Isilay Turan, and Ayca Kiykim. The first draft of the manuscript was written by Betul Gemici Karaaslan and Ayca Kiykim; all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ayca Kiykim.

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Ethics Approval

The study protocol was approved by the Istanbul University-Cerrahpasa, Institutional Ethics Committee (No: 06.07.2023–727977).

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Informed consent was obtained from the parents of all individual participants included in the study.

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Informed consent was obtained from the parents of all individual participants included in the study.

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The authors declare no competing interests.

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Karaaslan, B.G., Turan, I., Aydemir, S. et al. Neurologic Status of Patients with Purine Nucleoside Phosphorylase Deficiency Before and After Hematopoetic Stem Cell Transplantation. J Clin Immunol 43, 2062–2075 (2023). https://doi.org/10.1007/s10875-023-01585-6

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