Delayed Onset of (Severe) Combined Immunodeficiency (S)CID (T-B plus NK plus ): Complete IL-7 Receptor Deficiency in a 22 Months Old Girl
ABSTRACT Usually IL-7 receptor deficiency presents as (T-B+NK+) (Severe) Combined Immunodeficiency (SCID) within the first six months of life. All published IL-7R-deficient patients so far have been diagnosed and received stem cell transplantation within the first year of life.
We present a female patient born to non-consanguineous German parents with delayed manifestation. She presented with superinfected dermatitis at 6 months of life and developed a first pneumonia at age 9 months. On admission to our department at 22 months the patient presented with severe T cell lymphopenia. PNEUMOCYSTIS JIROVECI pneumonia was diagnosed from broncho-alveolar lavage fluid.
Sequencing of IL7RA in the patient revealed compound heterozygous mutations. FACS analysis showed no expression of IL-7 receptor alpha-chain on the patient's lympho- and monocytes. The patient successfully received haematopoietic stem cell transplantation from a 9/10 matched unrelated donor at age 24 months. CONLUSION: Despite almost absent T cell functions clinical symptoms occurred late compared to previously published patients. Thus even in patients with moderate clinical symptoms and delayed onset a (T-B+NK+) (Severe) Combined Immunodeficiency ((S)CID)) due to missing IL-7 receptor signalling must be considered.
Article: Diagnostik primärer Immundefekte[Show abstract] [Hide abstract]
ABSTRACT: Die Basisdiagnostik bei Verdacht auf Immundefekt soll die meisten lebensbedrohlichen und häufige immunologische Erkrankungen detektieren. Sie umfasst ein mikroskopisch differenziertes Blutbild und die Bestimmung von IgG, IgA, IgM und IgE (Ig: Immunglobulin). Ein SCID („severe combined immunodeficiency“) kann oft bereits anhand der meist (aber nicht immer!) vorhandenen Lymphopenie und dem Mangel an IgM diagnostiziert werden. Für CVID („common variable immunodeficiency“) sprechen ein persistierender IgG-Mangel nach Abschluss des 2. Lebensjahrs, ausgeschlossene sekundäre Ursachen des Antikörpermangels, 2 von 3 reduzierte Immunglobulinklassen und reduzierte Impfantikörpertiter. Durch diese immunologische Basisdiagnostik lassen sich vermutlich nur 40–50% der bisher bekannten Immundefekte erkennen. Die am klinischen Bild (Erreger, Art, Schwere und Verlauf der Infektion, syndromale Manifestationen, Zeichen einer gestörten Immunregulation) und den Ergebnissen der Basisdiagnostik ausgerichtete erweiterte immunologische Diagnostik ermöglicht eine Eingrenzung des Immundefekts. Die exakte Beschreibung des klinisch-immunologischen Phänotyps ist Voraussetzung für eine gezielte molekulargenetische Diagnostik.Monatsschrift Kinderheilkunde 05/2011; 159(5). DOI:10.1007/s00112-010-2332-z · 0.28 Impact Factor
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ABSTRACT: B+NK+SCID (severe combined immunodeficiency) due to IL7Rα deficiency represents approximately 10% of American SCID cases. To better understand the spectrum of autoimmune disorders associated with IL7Rα deficiency, we describe two unrelated IL7Rα-deficient female SCID infants whose clinical picture was dominated by autoimmune manifestations: one with intrauterine Omenn syndrome (OS) and another with persistent thrombocytopenic purpura since 4 months of age. The OS baby harbored a homozygous p.C118Y mutation in IL7R. She presented dense eosinophilic infiltrates in several organs, including pancarditis, which may have contributed to her death (on the 2nd day of life). B cells were observed in lymph nodes, spleen, bone marrow and thymus. The second patient harbored compound heterozygous p.C118Y and p.I121NfsX8 mutations. She underwent a successful unrelated cord blood transplant. In conclusion, early OS can be observed in patients with IL7R mutations, and autoimmune cytopenias could also complicate the clinical course of SCID babies with this type of defect.Human immunology 04/2014; DOI:10.1016/j.humimm.2014.04.006 · 2.28 Impact Factor