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At a glance

Extremely rare severe immune deficiency disorder characterized by T-cell deficiency with little or no abnormality of γ-globulin due to the underdevelopment of the thymus. Clinical features include failure to thrive, recurrent lung infections, and metaphyseal dysostosis.

Synonyms

Immune Defect Resulting from Absence of Thymus; Severe Combined Immunodeficiency, Nezelof Type; Thymus Absence Immune Defect Disease.

Incidence

Extremely rare, limited case reports only.

History

Genetic disorder first reported by C. Nezelof, a French pediatrician, in 1964.

Genetic inheritance

Autosomal recessive inheritance; some X-linked reports.

Pathophysiology

Abnormal expression of CD44 (an adhesion molecule, interacting with the matrix ligands hyaluronan and fibronectin) could interfere with normal thymocyte and thymic epithelial interaction, leading to abnormal thymocyte differentiation.

Diagnosis

Clinically evocated in patients with recurrent infections and normal humoral immunity.

Clinical aspects

Failure to thrive is common. Main clinical features can include metaphyseal dysostosis, chronic diarrhea, hepatosplenomegaly, eczematoid rash, and pyoderma. Recurrent pseudomonas and monilia infections are frequent, particularly bronchopulmonary infections. Bronchiectasis and emphysema are often observed. Susceptibility to viral infections. Immunologic features are remarkable: absent thymus, T-cell deficiency, impaired antibody synthesis, cellular immune defect, decreased lymphoid tissue while plasma cells are present, impaired delayed hypersensitivity with poor skin graft rejection. Humoral immunity is normal, as is the immunoglobulin level. Lymphopenia is observed.

Precautions before anesthesia

Evaluate immunologic status (obtain full, documented history of infection, complete immunologic status evaluation). Evaluate respiratory function (clinical, chest radiographs/CT, pulmonary function test, arterial blood gas analysis). Evaluate hydration and renal function in case of severe chronic diarrhea (clinical, laboratory tests, including urea and creatinine levels and electrolytes). Preoperative full blood count is recommended.

Anesthetic considerations

Strict asepsis is needed considering the immunity defect. Preoperative hydration correction might be necessary preoperatively. Perioperative respiratory monitoring and physiotherapy can be useful, and postoperative mechanical ventilatory support may be anticipated if necessary.

Pharmacological implications

Prophylactic antibiotics may be adapted to immunologic status and previous infections.

Other conditions to be considered

  • Bruton Agammaglobulinemia Tyrosine Kinase X-linked: Tonsillar system is absent.

  • Swiss-Type Agammaglobulinemia: Thymus and tonsillar system are absent.

  • DiGeorge Syndrome: Parathyroids and thymus are absent.

References

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Knutsen  AP, Wall  D, Mueller  KR, Bouhasin  JD: Abnormal in vitro thymocyte differentiation in a patient with severe combined immunodeficiency—Nezelof’s syndrome. J Clin Immunol 16:151, 1996.  [PubMed: 8734358]
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Nezelof  C, Jammet  M-L, Lortholary  P,  et al: L’hypoplasie hereditaire du thymus: sa place et sa responsabilite dans une observation d’aplasie lymphocytaire, normoplasmocytaire et normoglobulinemique du nourrisson. Arch Fr Pediatr 21:897, ...

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