Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A newborn infant presented with hepatosplenomegaly, rash, anemia, and leukocytosis at one day of age and manifested characteristic myeloid metaplasia by one mouth of life. Vitamin B12 and leukocyte alkaline phosphatase were elevated and platelet aggregation was impaired. Myelofibrosis was not present and neutrophil function was preserved. An unidentified high isoelectric point hemoglobin with unusual chromatographic and electrophoretic behaviors was found to comprise 12% of the total hemoglobin. The myeloid metaplasia and mutant hemoglobin disappeared over the subsequent months without biochemical or clinical residual. The available evidence was consistent with the mutant hemoglobin representing either a gamma chain or clonal embryonic chain variant. The inability to clarify prognostic factors in these unusual myeloproliferative syndromes suggests caution in the initiation of cytotoxic therapy.
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PMID:Transient myeloid metaplasia associated with an unusual hemoglobin in a newborn infant. 9 73

A 53-year-old woman was admitted to our hospital on Nov. 16, 1987, because of general fatigue. On admission, she had hepatosplenomegaly and her peripheral blood profile showed a white blood cell count (WBC) of 309 x 10(3)/microliters with immature neutrophils, a hemoglobin level (Hb) of 7.6 g/dl, platelet count (PLT) of 536 x 10(3)/microliters, neutrophilic alkaline phosphatase (NAP) score of 44. Both Vitamin B12 and LDH levels were high. The bone marrow showed marked myeloid hyperplasia. In a cytogenetic study, Ph1 was found in 3 of 8 metaphases and Ph1 with an additional abnormality of 8 trisomy was noted in 5 of 8 metaphases. She was diagnosed as having chronic myelogenous leukemia (CML) and treated by i.m. injection of interferon (IFN)-alpha at a daily dose of 6 x 10(6) U. Administration of IFN-alpha induced fever for a few days. WBC, PLT count and LDH level gradually decreased, and the NAP score and hepatosplenomegaly improved. She achieved remission in February, 1988. Administration of IFN-alpha was stopped in April, 1988, when the bone marrow showed hypocellularity and normal karyotype. She was treated with 20 mg of prednisolone daily from May until August, because of progressive pancytopenia. She had received no treatment until July, 1989. In May, 1989, the bone marrow again showed myeloid hyperplasia and Ph1 was found in all cells analyzed. Therefore, we resumed IFN-alpha treatment. It is interesting that remission of CML continues for more than one year after discontinuation of IFN-alpha in this case.
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PMID:[One-year remission of chronic myelogenous leukemia (CML) after discontinuation of interferon-alpha]. 221 81

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