Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Physicians caring for infants in the first months of life need to know the normal ranges for absolute lymphocyte counts (ALCs) during that age. Any ALC <2500/microL is potentially pathogenic in early infancy and should be evaluated. We report the case of a 4-month-old white girl with a 2-month history of an oral ulcer, intermittent fever, recurrent otitis, decreased appetite, weight loss, and a new respiratory illness with hypoxemia. She had been in an in-home day care since birth. The patient's primary care physician had seen her frequently and obtained blood counts, but her persistent lymphopenia had not been appreciated. The infant was ultimately diagnosed with T(-)B(-)NK(+) (lacking both B and T lymphocytes and having primarily natural killer [NK] cells), recombinase-activating gene 2 (RAG2)-deficient severe combined immunodeficiency (SCID). However, because she had already developed 2 difficult-to-treat viral infections (parainfluenza 3 and adenovirus), she did not survive long enough to receive a bone marrow transplant. Newborn screening would not only have made the diagnosis at birth but would have led to measures to protect her from becoming infected before she could receive a transplant. Newborn screening would also reveal the true incidence of SCID and define the range of conditions characterized by severely impaired T-cell development. Until screening for SCID and other T-cell defects becomes available for all neonates (either by quantifying T-cell receptor excision circles in Guthrie spots or using other tests that quantify T cells), all pediatricians should know the normal range for ALCs according to age. Recognition of the characteristic lymphopenia of SCID can facilitate early diagnosis.
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PMID:Why newborn screening for severe combined immunodeficiency is essential: a case report. 2060 53

Serine/threonine kinase 4 (STK4) deficiency is an autosomal recessive genetic condition that leads to primary immunodeficiency (PID) typically characterized by lymphopenia, recurrent infections and Epstein Barr Virus (EBV) induced lymphoproliferation and -lymphoma. State-of-the-art treatment regimens consist of prevention or treatment of infections, immunoglobulin substitution (IVIG) and restoration of the immune system by hematopoietic stem cell transplantation. Here, we report on two patients from two consanguineous families of Turkish (patient P1) and Moroccan (patient P2) decent, with PID due to homozygous STK4 mutations. P1 harbored a previously reported frameshift (c.1103 delT, p.M368RfsX2) and P2 a novel splice donor site mutation (P2; c.525+2 T>G). Both patients presented in childhood with recurrent infections, CD4 lymphopenia and dysregulated immunoglobulin levels. Patient P1 developed a highly malignant B cell lymphoma at the age of 10 years and a second, independent Hodgkin lymphoma 5 years later. To our knowledge she is the first STK4 deficient case reported who developed lymphoma in the absence of detectable EBV or other common viruses. Lymphoma development may be due to the lacking tumor suppressive function of STK4 or the perturbed immune surveillance due to the lack of CD4+ T cells. Our data should raise physicians' awareness of [1] lymphoma proneness of STK4 deficient patients even in the absence of EBV infection and [2] possibly underlying STK4 deficiency in pediatric patients with a history of recurrent infections, CD4 lymphopenia and lymphoma and unknown genetic make-up. Patient P2 experienced recurrent otitis in childhood, but when she presented at the age of 14, she showed clinical and immunological characteristics similar to patients suffering from Autoimmune Lymphoproliferative Syndrome (ALPS): elevated DNT cell number, non-malignant lymphadenopathy and hepatosplenomegaly, hematolytic anemia, hypergammaglobulinemia. Also patient P1 presented with ALPS-like features (lymphadenopathy, elevated DNT cell number and increased Vitamin B12 levels) and both were initially clinically diagnosed as ALPS-like. Closer examination of P2, however, revealed active EBV infection and genetic testing identified a novel STK4 mutation. None of the patients harbored typically ALPS-associated mutations of the Fas receptor mediated apoptotic pathway and Fas-mediated apoptosis was not affected. The presented case reports extend the clinical spectrum of STK4 deficiency.
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PMID:EBV Negative Lymphoma and Autoimmune Lymphoproliferative Syndrome Like Phenotype Extend the Clinical Spectrum of Primary Immunodeficiency Caused by STK4 Deficiency. 3038 45