The Broad Clinical Spectrum and Transplant Results of PNP Deficiency

Dinur-Schejter, Yael; Even‐Or, Ehud; Shadur, Bella; NaserEddin, Adeeb; Stepensky, Polina; Zaidman, Irina

doi:10.1007/s10875-019-00698-1

Cited by 10 publications

(7 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clearly, larger HSCT series with long-term outcome data are lacking. Moreover, in the preexisting literature, no clear genotype-phenotype correlations were shown for the neurological outcome and the development of the children is also influenced by the acquired infections [ 9 ]. Thus, it is impossible to gauge the neurological outcome in a single patient and it is difficult to evaluate the effect of therapeutic interventions.…”

mentioning

confidence: 99%

Upfront Enzyme Replacement via Erythrocyte Transfusions for PNP Deficiency

et al. 2021

View full text Add to dashboard Cite

mentioning

confidence: 99%

Upfront Enzyme Replacement via Erythrocyte Transfusions for PNP Deficiency

et al. 2021

View full text Add to dashboard Cite

“…Hypoplasia of the thymus and altered T cell selection occur, likely due to toxic levels of these purine metabolites. A wide variety of bacterial and viral infections can ensue, including disseminated Epstein-Barr virus and cytomegalovirus infections ( 1 – 3 ), with poor prognosis. Other organ systems are also affected.…”

Section: Autoimmune Diseases In the Context Of Immune Deficienciesmentioning

confidence: 99%

“…In the brain, a neuronal apoptosis pathway that is magnified in the absence of PNP may explain neurological symptoms ( 1 – 4 ). Allogeneic hematopoietic stem cell transplant has been reported to at least partly alleviate the neurological aspects of PNP deficiency while reconstituting T cell immunity ( 1 – 3 ). Protein replacement strategies and gene therapy are also being explored ( 1 , 5 ).…”

Section: Autoimmune Diseases In the Context Of Immune Deficienciesmentioning

confidence: 99%

Immunodeficiency and autoimmunity: companions not opposites

Fox¹

2022

Journal of Clinical Investigation

View full text Add to dashboard Cite

Autoimmunity has long been regarded as the polar opposite of immunodeficiency, but clinical and experimental evidence refute this notion. Indeed, numerous inborn or acquired immunodeficiency syndromes are characterized by the development of autoimmune complications in the setting of deficient immune defenses against microbial pathogens. Appreciation that much of the daily business of a healthy immune system is the avoidance of potentially harmful responses to innocuous environmental antigens or components of the host organism helps provide a context for these observations. In this issue of the JCI , Abt and colleagues report on purine nucleoside phosphorylase (PNP) deficiency, exploring the basis for the autoimmune complications that develop in this particular form of T cell immune deficiency and assigning a key role for overactivation of TLR7.

show abstract

“…The phenotype is profound T-cell de ciency with variable B-and NK-cell functions and results in recurrent and persistent infections that typically begin in the rst year of life. Patients account for approximately 4% of all patients with severe combined immunode ciency (SCID) 4 . Patients present with autoimmune manifestations, neutropenia, neurologic abnormalities, or infections resembling those of SCID or combined immunode ciency [5][6][7][8][9][10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

“…Autoimmune manifestations often include autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) 4,13,14,16 . Hematologic malignancies have also been reported in PNP patients 17,18 .…”

Section: Introductionmentioning

confidence: 99%

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

Karaaslan¹,

Turan²,

Aydemir³

et al. 2023

Preprint

View full text Add to dashboard Cite

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.

show abstract

The Broad Clinical Spectrum and Transplant Results of PNP Deficiency

Cited by 10 publications

References 34 publications

Upfront Enzyme Replacement via Erythrocyte Transfusions for PNP Deficiency

Upfront Enzyme Replacement via Erythrocyte Transfusions for PNP Deficiency

Immunodeficiency and autoimmunity: companions not opposites

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

Contact Info

Product

Resources

About