Purine Nucleoside Phosphorylase Deficiency Follow-up

  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD   more...
 
Updated: Aug 29, 2011
 

Further Inpatient Care

  • Patients with adenosine deaminase (ADA) deficiency or purine nucleoside phosphorylase (PNP) deficiency who have acute infections may require hospitalization for diagnostic studies to identify opportunistic pathogens.
  • For stem cell reconstitution, patients are typically hospitalized in single-occupancy protective reverse-isolation rooms with high-efficiency particulate air-filtration systems. Patients should remain in isolation until engraftment is evident.
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Further Outpatient Care

  • Intravenous immunoglobulin (IVIG) therapy is typically continued for 6-12 months after bone marrow transplantation. Reimmunization of the patient begins approximately 1 year after transplantation. Live viral vaccines should be avoided.
  • Bone marrow transplantation does not correct the neurologic problems associated with purine nucleoside phosphorylase deficiency. Ongoing therapy for these problems should continue.
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Prognosis

  • The patient's prognosis depends on the success of immune reconstitution of the T-cell and B-cell systems.
  • If immune reconstitution is successful, the patient's prognosis is good. However, bone marrow transplantation does not correct the neurologic disease.
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Patient Education

  • Genetic counseling: Purine nucleoside phosphorylase deficiency is an autosomal recessive inherited immunodeficiency. If purine nucleoside phosphorylase deficiency is diagnosed in a child, the parents have a 25% risk of having affected children in subsequent pregnancies.
  • Prenatal diagnosis: Prenatal diagnosis can be performed (see Special Concerns below).
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Contributor Information and Disclosures
Author

Alan P Knutsen, MD  Professor of Pediatrics, Director of Pediatric Allergy and Immunology, Director Jeffrey Modell Diagnostic & Research Center for Primary Immuodeficiences (CGCMC), Director of Pediatric Clinical Immunology Laboratory, Department of Pathology, St Louis University Health Sciences Center

Alan P Knutsen, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, and Clinical Immunology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Ann O'Neill Shigeoka, MD †  Former Clinical Associate Professor, Department of Pediatrics, Division of Immunology-Rheumatology, University of Utah School of Medicine

Ann O'Neill Shigeoka, MD † is a member of the following medical societies: American Federation for Medical Research, Clinical Immunology Society, Pediatric Infectious Diseases Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David J Valacer, MD  Consulting Staff, Hoffman La Roche Pharmaceuticals

David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American Thoracic Society, and New York Academy of Sciences

Disclosure: Nothing to disclose.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville School of Medicine

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD  Associate Professor, Division of Pulmonary, Allergy/Immunology, and Infectious Diseases, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Mucosal Immunology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

References

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Biochemical pathway of purine metabolism. AMP = adenosine monophosphate, APRT = adenine phosphoribosyltransferase, GMP = guanosine monophosphate, HGPRT = hypoxanthine-guanine phosphoribosyltransferase, IMP = inosine monophosphate, NP = nucleoside phosphorylase, PPriboseP = 5-phosphorylribose-1-pyrophosphate.
Table 1. Immunologic Studies and Findings in Adenosine Deaminase Deficiency
StudyInfantile OnsetLate OnsetAdult Onset
LymphopeniaMarkedly decreasedDecreasedDecreased
CD3+ cellsAbsent or traceMarkedly reducedMarkedly reduced
CD4/CD8 ratioToo few to test< 1< 1
Phytohemagglutinin responseAbsentReducedReduced
Antigen responseAbsentTraceTrace
Mixed lymphocyte culture responseReduced......
Ig responseAbsentLow to absentNormal (low IgG2)
IgELowElevatedElevated
Antibody responseAbsentAbsent to lowLow to polysaccharides antigens
EosinophiliaRareCommonCommon
InfectionsPredominantly viral, fungal, opportunistic, bacterialBacterial sinopulmonaryBacterial sinopulmonary, varicella-zoster, herpes simplex, candidal
Table 2. Intravenous Immunoglobulin[28, 29, 30]
Brand (Manufacturer)Manufacturing ProcesspHAdditives*Parenteral Form and Final ConcentrationIgA Content (mcg/mL)
Carimune NF (CSL Behring)Kistler-Nitschmann fractionation; pH 4, nanofiltration6.4-6.86% solution: 10% sucrose < 20 mg NaCl/g proteinLyophilized powder 3%, 6%, 9%, 12%Trace
Flebogamma (Grifols USA)Cohn-Oncley fractionation, polyethyline glycol (PEG) precipitation, ion-exchange chromatography, pasteurization5.1-6Sucrose-free, contains 5% D-sorbitolLiquid 5%< 50
Gamunex (Talecris Biotherapeutics)Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation4-4.5Contains no sugar, contains glycineLiquid 10%46
Iveegam EN (Baxter Bioscience)Cohn-Oncley fraction II/III; ultrafiltration; pasteurization6.4-7.25% solution: 5% glucose, 0.3% NaClLyophilized powder 5%< 10
Gammagard S/D, Polygam S/D (Baxter Bioscience for the American Red Cross)Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation 6.4-7.25% solution: 0.3% albumin, 2.25% glycine, 2% glucoseLyophylized powder 5%, 10%< 1.6 (5% solution)
Gammagard Liquid 10%



(Baxter Bioscience)



Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation 4.6-5.10.25M glycineReady-for-use Liquid 10%37
Octagam (Octapharma USA)Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization5.1-610% maltoseLiquid 5%200
Panglobulin (Swiss Red Cross for the American Red Cross)Kistler-Nitschmann fractionation; pH 4, trace pepsin, nanofiltration6.6Per gram of IgG: 1.67 g sucrose, < 20 mg NaClLyophilized powder 3%, 6%, 9%, 12%720
Privigen Liquid 10%



(CSL Behring)



Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration4.6-5L-proline (~250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizersReady-for use liquid 10%< 25
*IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors (eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs).
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