Purine Nucleoside Phosphorylase Deficiency Differential Diagnoses

Updated: Aug 07, 2019
  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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Diagnostic Considerations

Because multiple genetic and metabolic disorders can cause combined immunodeficiency (CID), PNP deficiency should be included in the evaluation when the patient's clinical history and physical findings suggest severe combined T-cell and B-cell immunodeficiency.

PNP deficiency may be misdiagnosed as thymic dysplasia (Nezelof syndrome). In both disorders, lymphopenia is observed, with decreased T-cell numbers but normal numbers of B cells, and specific antibody deficiency with normal serum immunoglobulin (Ig) levels is present. However, autoimmune complications and neurologic symptoms are more likely to occur in patients with PNP deficiency than in those with Nezelof syndrome.

Because of the recurrent bacterial sinopulmonary infections, PNP deficiency may also be misdiagnosed as B-cell immunodeficiencies, such as common variable immunodeficiency (CVID), hyper–immunoglobulin M (IgM) syndrome, or Bruton agammaglobulinemia. However, in contrast to PNP deficiency, these primary B-cell immunodeficiencies are typically characterized by profound decrease in serum Ig levels. In variants of ADA and PNP deficiencies, in which the clinical picture resembles predominant B-cell immunodeficiency (eg, CVID, Bruton agammaglobulinemia), the presence of lymphopenia, especially T lymphopenia, may provide a clinical clue.

Lymphopenia should prompt an evaluation for both ADA and PNP deficiencies. DiGeorge anomaly (DGA) also causes variably decreased numbers of T cells, normal B-cell numbers, and normal serum Ig levels with variably deficient antibody responses. Physical examination usually reveals facial dysmorphism, including low-set ears, hypognathia, and hypertelorism in DGA patients. Conotruncal cardiac defects may or may not be present in DGA. Monosomic deletion of 22q11.2 is present in more than 95% patients with DGA and can be identified by fluorescence in situ hybridization (FISH) analysis or microarray analysis.

Differential Diagnoses

  • Severe Combined Immunodeficiency