The immunodeficiency is progressive with normal immune functions at birth, but then, T-cell deficiency with variable B-cell functions usually presents by the age of two yr. [ncbi.nlm.nih.gov]

Patients present with predominantly T-lymphocytopenia, and the immunological presentation characteristically is later than patients with classical severe combined immunodeficiency (SCID) ( 4 ). [journal.frontiersin.org]

• Anemia

  We describe a five-yr-old boy with muscular hypertonia, impaired growth, autoimmune hemolytic anemia, and neutropenia who underwent HSCT from his HLA-identical sister. [ncbi.nlm.nih.gov]

  Differential diagnosis Differential diagnosis includes aplastic anemias, SCID, severe combined immunodeficiency due to adenosine deaminase deficiency, ataxia-telangiectasia (see these terms), and viral meningoencephalitis. [orpha.net]

  […] deoxyGTP, resulting in immune dysfunction by inhibiting ribonucleotide reductase, and blocking cell division, causing predominantly T-cell immune dysfunction Clinical Recurring opportunistic infections of lungs, skin, GU tract, autoimmune hemolytic anemia [medical-dictionary.thefreedictionary.com]

• Fever

  Abstract A 2 1/2-year-old boy presented with an illness resembling glandular fever. He was found to have T-cell deficiency with lack of red and white cell purine nucleoside phosphorylase enzyme activity. A spastic tetraparesis was noted. [ncbi.nlm.nih.gov]

  From birth, Finn Stever has struggled with illnesses and developmental delays, including countless viral rashes, fevers over 106, chicken pox, shingles, chronic diarrhea, chronic ear infections, not being able to eat solid foods, not being able to roll [mycentraljersey.com]

• Splenomegaly

  If the proliferation to antigen was not performed, but at least 4 of the following 10 supportive criteria, at least one of which must be among those marked with an asterisk (*) are present, the patient is eligible: hepatomegaly; splenomegaly; lymphadenopathy [clinicaltrials.gov]

  We anticipated that effective treatment and correction of the immune defects in PNP –/– mice would subsequently prevent the splenomegaly, weight loss and early death. [doi.org]

• Failure to Thrive

  The characteristic features of the disease include severe T cell immune defects with recurrent infections, a failure to thrive, and progressive neurological findings. [ncbi.nlm.nih.gov]

  Failure to thrive has also been reported. Up to 2/3 of patients have neurologic involvement including motor system dysfunction, hyper/hypotonia, spastic paresis, ataxia, hyperactivity, and behavioral problems. [orpha.net]

  In addition, failure to thrive eventually ensues. The risk of lymphoma is also increased in patients with PNP deficiency. [emedicine.com]

• Nausea

  “The chemotherapy has caused all of the traditional symptoms it is associated with, baldness, nausea, mouth sores and most likely he will never be able to have children of his own, but it is a small price to pay, considering the alternative. [mycentraljersey.com]

• Muscle Spasticity

  Purine nucleoside phosphorylase deficiency can be also associated with neurologic symptoms, including mental retardation and muscle spasticity, and increased risk of autoimmune disorders. [novocib.com]

  Some people with this condition develop neurologic symptoms, such as stiff or rigid muscles ( spasticity ), uncoordinated movements ( ataxia ), developmental delay, and intellectual disability. [1] [2] [3] In addition, PNP deficiency is associated with [rarediseases.info.nih.gov]

  This is especially prevalent in PNP deficiency with neurologic symptoms, including mental retardation and muscle spasticity, reported in 67% of patients with PNP deficiency. [emedicine.com]

• Behavior Disorder

  Deficiency of purine nucleoside phosphorylase (PNP) was detected in a 3-yr-old boy who was admitted for investigation of a behavior disorder and spastic diplegia. [ncbi.nlm.nih.gov]

  Abstract Deficiency of purine nucleoside phosphorylase (PNP) was detected in a 3-yr-old boy who was admitted for investigation of a behavior disorder and spastic diplegia. [pubmed.ncbi.nlm.nih.gov]

• Neurologic Manifestation

  PNP deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency, autoimmune hemolytic anemia, and by a complex of neurologic manifestations including ataxia, developmental delay, and spasticity. [ncbi.nlm.nih.gov]

  PMID: 24972650 Primary immunodeficiency diseases associated with neurologic manifestations. Dehkordy SF, Aghamohammadi A, Ochs HD, Rezaei N. Dehkordy SF, et al. J Clin Immunol. 2012 Feb;32(1):1-24. doi: 10.1007/s10875-011-9593-8. Epub 2011 Oct 26. [pubmed.ncbi.nlm.nih.gov]

• Lymphopenia

  There is severe lymphopenia with decreased absolute numbers of T and B lymphocytes. Mitogen-stimulated blastogenesis is reduced, but response to allogeneic lymphocytes is normal. A monoclonal IgG protein is present. [ncbi.nlm.nih.gov]

  Lack of PNP allows intracellular accumulation of such metabolites which are particularly toxic to immature lymphoid cells, leading to lymphopenia and impaired cell-mediated immunity. [orpha.net]

• Hypouricemia

  In five of the seven patients, plasma uric acid was found to be within the pediatric normal range, suggesting that PNPase deficiency should not be ruled out in the absence of hypouricemia. [ncbi.nlm.nih.gov]

Results from this clinical trial will have implications not only for the treatment of PNP deficiency but for the treatment of other immunodeficiencies as well. [iths.pure.elsevier.com]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

TAT-PNP treatment restores uric acid production in PNP –/– mice. [doi.org]

Treatment of adenosine deaminase deficiency is by bone marrow or stem cell transplantation and enzyme replacement therapy. Somatic cell gene therapy is being evaluated as well. [merckmanuals.com]

Treatment of xanthine oxidase deficiency is high fluid intake to minimize likelihood of stone formation and allopurinol in some patients. Click here for Patient Education [msdmanuals.com]

PNP deficiency has a grave prognosis. No patient has reached the third decade of life. Twenty-nine of the 33 reported patients have died from their disease. Prenatal diagnosis is currently available. [ncbi.nlm.nih.gov]

Prognosis If left untreated, prognosis is poor and patients usually die in the first decade of life, often succumbing to infections. [orpha.net]

If left untreated, PNP deficiency usually causes death during the first or second decade of life due to recurrent infections. [4] Treatment with a bone marrow transplant may cure the immune system problems and improve the prognosis. [rarediseases.info.nih.gov]

Etiology PNP deficiency is caused by loss-of-function mutations in the PNP gene (14q11.2) which encodes a key enzyme (PNP) in the purine salvage pathway. [orpha.net]

Acetylation, Phosphoprotein Proteomic databases 2D gel databases PTM databases Expression i Tissue specificity i Expressed in red blood cells; overexpressed in red blood cells (cytoplasm) of patients with hereditary non-spherocytic hemolytic anemia of unknown etiology [uniprot.org]

Summary Epidemiology To date, less than 70 cases have been reported in the world literature. PNP deficiency accounts for approximately 4% of patients with severe combined immunodeficiency (SCID; see this term). [orpha.net]

You can help by adding to it. ( June 2017 ) Epidemiology [ edit ] PNP-deficiency is extremely rare. [en.wikipedia.org]

Epidemiology PNP-deficiency is extremely rare. [ipfs.io]

Relevant External Links for PNP Human Genome Epidemiology (HuGE) Navigator PNP Atlas of Genetics and Cytogenetics in Oncology and Haematology: PNP No data available for Genatlas for PNP Gene Genetic variation in genes associated with arsenic metabolism [genecards.org]

Because only small amounts of adenosine deaminase are necessary for competent immunity, some patients with ADA mutations may still have 8-42% adenosine deaminase activity and no profound immunodeficiency. [2, 3] Epidemiology Frequency United States PNP [emedicine.com]

Cause, Pathophysiology and Genetics Purine nucleoside phosphorylase deficiency has an autosomal recessive pattern of inheritance. [ipfs.io]

Pathophysiology PNP is an enzyme in the purine salvage pathway that metabolizes inosine and guanosine to hypoxanthine. [4, 5, 6, 7] In the preceding step of the pathway, ADA metabolizes adenosine to inosine. [emedicine.com]

Deoxyguanosine kinase activity was specifically measured by using an anti-NP antibody to prevent alternative-product formation. [biochemj.org]

Figure 6 Treatment of PNP –/– mice with TAT-PNP prevents abnormalities in thymus and T lymphocyte number and function. [doi.org]