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TAP deficiency syndrome
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TAP deficiency syndrome

Contributors: Reba Suri MD, Eric Ingerowski MD, FAAP, Susan Burgin MD
Other Resources UpToDate PubMed

Synopsis

Transporter associated with antigen processing (TAP) deficiency syndrome, the most well-characterized condition among the type I bare lymphocyte syndromes (BLS), is a rare autosomal recessive primary immunodeficiency disorder due to a defect within the TAP complex. The TAP complex, a heterodimer consisting of 2 subunits (TAP1 and TAP2) synthesized from genes located on the human leukocyte antigen (HLA) locus of chromosome 6, is involved in the processing and subsequent presentation of antigenic peptides via cell-surface major histocompatibility complex (MHC) class I molecules during the immune response. Deletion or mutation of the genes encoding either subunit of the TAP complex results in impaired antigenic processing and down-regulation of MHC class I expression on the surface of lymphocytes. The resulting impaired immune response leads to increased susceptibility to bacterial infections.

Patients with TAP deficiency syndrome typically present with recurrent bacterial infections of the upper respiratory tract (chronic purulent rhinitis, sinusitis, otitis media) within the first 6 years of life. This is followed by recurrent bacterial infections of the lower respiratory tract (bacterial pneumonia, chronic bronchitis, and subsequent bronchiectasis) and skin (necrotizing granulomatous lesions) within the second decade of life. Common culprits include both gram positive (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae) and gram negative (Klebsiella, Escherichia coli, Pseudomonas aeruginosa) organisms. Early age of onset and a positive family history can be additional diagnostic clues.

If left untreated, recurrent respiratory infections with subsequent bronchiectasis and progressive respiratory failure may significantly increase morbidity and mortality. Septicemia is an additional complication.

Codes

ICD10CM:
D81.6 – Major histocompatibility complex class I deficiency

SNOMEDCT:
725136003 – Immunodeficiency by defective expression of human leukocyte antigen class 1

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

  • Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) can also present with necrotizing granulomatous inflammation of the skin and upper respiratory tract, but, unlike TAP deficiency syndrome, GPA classically also affects the kidneys, leading to hematuria with red cell casts on evaluation. Positivity for cytoplasmic antineutrophil cytoplasmic autoantibodies (c-ANCA) / proteinase 3 (PR3)-ANCA can also be used to differentiate this condition.
  • Chronic granulomatous disease (CGD) can also present with cutaneous and respiratory granulomatous inflammation, and affected individuals have increased susceptibility to infection with catalase positive organisms. An abnormal dihydrorhodamine test or nitroblue tetrazolium dye reduction test can be used to diagnose this condition.
  • Common variable immunodeficiency (CVID) involves defective B cell differentiation and subsequent decreased plasma cell formation and immunoglobulin synthesis. CVID can also present with recurrent bacterial respiratory and cutaneous infections. Flow cytometry for HLA expression and serum electrophoresis can be used to differentiate this condition.
  • Leukocyte adhesion deficiency type 1 – Omphalitis, delayed separation of the umbilical cord stump at birth, recurrent otitis media, perirectal abscesses, bacterial sepsis, and necrotizing ulcers resembling pyoderma gangrenosum.
  • Sarcoidosis
  • Tuberculosis
  • Nocardiosis (see cutaneous nocardiosis, pulmonary nocardiosis)
  • Leishmaniasis (see Old World cutaneous leishmaniasis, New World cutaneous leishmaniasis)
  • Cystic fibrosis – Sweat chloride concentration would not be elevated in TAP deficiency syndrome and can be used to differentiate this condition.
  • Primary ciliary dyskinesia
  • Midline granuloma
  • Pyoderma gangrenosum (PG) is a diagnosis of exclusion.

Best Tests

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Therapy

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References

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Last Reviewed:07/08/2020
Last Updated:07/27/2020
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TAP deficiency syndrome
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TAP deficiency syndrome
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