hypergammaglobulinemia

Summary

Summary: An excess of GAMMA-GLOBULINS in the serum due to chronic infections or PARAPROTEINEMIAS.

Top Publications

  1. Groeneweg M, Hartwig N, Poerink Stockschläder A, Schweizer J, Bijleveld C, Bredius R. [Two children with severe recurrent infections and the X-linked hyper-IgM syndrome]. Ned Tijdschr Geneeskd. 2003;147:1024-8 pubmed
    ..In a child with severe recurrent infections, and with dysgammaglobulinaemia with a normal or increased IgM level, the diagnosis of 'X-linked hyper-IgM syndrome' should be considered. ..
  2. Stojanov S, Lohse P, Lohse P, Hoffmann F, Renner E, Zellerer S, et al. Molecular analysis of the MVK and TNFRSF1A genes in patients with a clinical presentation typical of the hyperimmunoglobulinemia D with periodic fever syndrome: a low-penetrance TNFRSF1A variant in a heterozygous MVK carrier possibly influences the p. Arthritis Rheum. 2004;50:1951-8 pubmed
  3. Haas D, Kelley R, Hoffmann G. Inherited disorders of cholesterol biosynthesis. Neuropediatrics. 2001;32:113-22 pubmed
    ..Rational therapeutic approaches have been described for HIDS, MVA and Smith-Lemli-Opitz syndrome. ..
  4. Frenkel J, Houten S, Waterham H, Wanders R, Rijkers G, Duran M, et al. Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D. Rheumatology (Oxford). 2001;40:579-84 pubmed
    ..Periodic fever and elevated IgD can result from other, still unknown, causes. Hence, testing for MK deficiency is necessary in patients with unexplained periodic fever. ..
  5. Alyahya G, Prause J, Heegaard S. Castleman's disease in the orbit. A 20-year follow-up. Acta Ophthalmol Scand. 2002;80:540-2 pubmed
    ..The successful medical treatment suggests that such a regime may substitute for surgery when the latter proves difficult. ..
  6. Ko H, Yang H, Yang J, Seo S, Chang S, Seong J, et al. Expansion of Tfh-like cells during chronic Salmonella exposure mediates the generation of autoimmune hypergammaglobulinemia in MyD88-deficient mice. Eur J Immunol. 2012;42:618-28 pubmed publisher
    ..Infection was accompanied by enlarged germinal centers and hypergammaglobulinemia with anti-double-stranded DNA (dsDNA)-specific Ab in sera, and the deposition of immune complexes in the ..
  7. Christianson G, Brooks W, Vekasi S, Manolfi E, Niles J, Roopenian S, et al. Beta 2-microglobulin-deficient mice are protected from hypergammaglobulinemia and have defective antibody responses because of increased IgG catabolism. J Immunol. 1997;159:4781-92 pubmed
    ..was preferential to IgG isotypes, and was greatly exaggerated in aging mice that normally develop hypergammaglobulinemia. Beta 2m-deficient mice, regardless of genetic background, also displayed a substantial reduction of ..
  8. Frenkel J, Willemsen M, Weemaes C, Dorland L, Mayatepek E. Increased urinary leukotriene E(4) during febrile attacks in the hyperimmunoglobulinaemia D and periodic fever syndrome. Arch Dis Child. 2001;85:158-9 pubmed
    ..As no effective treatment is yet available, leukotriene receptor antagonists might offer a new therapeutic approach for patients with the hyperimmunoglobulinaemia D and periodic fever syndrome. ..
  9. Vaiopoulos G, Sideris P, Anargyrou K, Melas P, Plessas N, Konstantopoulos K. Transient monoclonal hypergammaglobulinemia during the course of a rickettsia infection. Infection. 2002;30:249-50 pubmed

More Information

Publications62

  1. Prietsch V, Mayatepek E, Krastel H, Haas D, Zundel D, Waterham H, et al. Mevalonate kinase deficiency: enlarging the clinical and biochemical spectrum. Pediatrics. 2003;111:258-61 pubmed
    ..Recurrent febrile crises seem to diminish with increasing age and may not even be an obligatory finding. Elevation of IgD is most likely a secondary phenomenon that seems to be linked to recurrent febrile crises. ..
  2. De Milito A, Nilsson A, Titanji K, Thorstensson R, Reizenstein E, Narita M, et al. Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection. Blood. 2004;103:2180-6 pubmed
    b>Hypergammaglobulinemia and defective humoral immunity are hallmarks of HIV-1 infection. Naive B cells have been recently suggested as the major source of hypergammaglobulinemia in chronic viral infections...
  3. Simon A, Drewe E, Van der Meer J, Powell R, Kelley R, Stalenhoef A, et al. Simvastatin treatment for inflammatory attacks of the hyperimmunoglobulinemia D and periodic fever syndrome. Clin Pharmacol Ther. 2004;75:476-83 pubmed
    ..These data offer preliminary evidence for the hypothesis that simvastatin may improve inflammatory attacks in the hyper-IgD syndrome. This highlights the anti-inflammatory properties of HMG-CoA reductase inhibition. ..
  4. Bodar E, van der Hilst J, Drenth J, van der Meer J, Simon A. Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD syndrome: introducing a vaccination provocation model. Neth J Med. 2005;63:260-4 pubmed
    ..In this patient, the IL-1ra analogue anakinra was more successful in aborting the inflammatory attack than etanercept. We propose that this vaccination model will allow evaluation of treatment-on-demand in a controlled setting. ..
  5. Niitsu N, Kohri M, Hayama M, Nakamine H, Nakamura N, Bessho M, et al. Primary pulmonary plasmacytoma involving bilateral lungs and marked hypergammaglobulinemia: differentiation from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Leuk Res. 2005;29:1361-4 pubmed
    ..The effectiveness of the chemotherapy could confirm our diagnosis, although MALT-type lymphoma with plasmacytic differentiation cannot be completely ruled out...
  6. Houten S, Frenkel J, Rijkers G, Wanders R, Kuis W, Waterham H. Temperature dependence of mutant mevalonate kinase activity as a pathogenic factor in hyper-IgD and periodic fever syndrome. Hum Mol Genet. 2002;11:3115-24 pubmed
    ..Our results suggest that minor elevations in temperature can set off a chain of events with MK becoming progressively rate-limiting, leading to a temporary deficiency of isoprenoid end-products, which induces inflammation and fever. ..
  7. Khawaja K, Gennery A, Flood T, Abinun M, Cant A. Bone marrow transplantation for CD40 ligand deficiency: a single centre experience. Arch Dis Child. 2001;84:508-11 pubmed
    ..Bone marrow transplantation can be curative in CD40L deficiency. Better outcome is associated with younger age at transplantation and normal liver histology. ..
  8. Klasen I, Göertz J, van de Wiel G, Weemaes C, van der Meer J, Drenth J. Hyper-immunoglobulin A in the hyperimmunoglobulinemia D syndrome. Clin Diagn Lab Immunol. 2001;8:58-61 pubmed
    ..These results indicate a continuous, presumably systemic, stimulation of IgA in HIDS patients. ..
  9. O Gorman M, Zaas D, Paniagua M, Corrochano V, Scholl P, Pachman L. Development of a rapid whole blood flow cytometry procedure for the diagnosis of X-linked hyper-IgM syndrome patients and carriers. Clin Immunol Immunopathol. 1997;85:172-81 pubmed
    ..This is the first report of a whole blood procedure adapted for routine clinical use which is able to detect abnormal CD40L expression in XHIM patients and carriers. ..
  10. Hollenbaugh D, Wu L, Ochs H, Nonoyama S, Grosmaire L, Ledbetter J, et al. The random inactivation of the X chromosome carrying the defective gene responsible for X-linked hyper IgM syndrome (X-HIM) in female carriers of HIGM1. J Clin Invest. 1994;94:616-22 pubmed
    ..Unlike some other X-linked defects where extreme Lyonization may lead to disease, a small population of cells expressing the wild-type gp39 is sufficient to maintain normal humoral immunity and prevent the clinical symptoms of X-HIM. ..
  11. Houten S, Kuis W, Duran M, de Koning T, van Royen Kerkhof A, Romeijn G, et al. Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nat Genet. 1999;22:175-7 pubmed
    ..Moreover, immunoblot analysis demonstrated a deficiency of MK protein in patient fibroblasts, indicating a protein-destabilizing effect of the mutations. ..
  12. McDonnell T, Deane N, Platt F, Nunez G, Jaeger U, McKearn J, et al. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell. 1989;57:79-88 pubmed
    ..bcl-2-Ig transgenic mice document a prospective role for the t(14;18) in B cell growth and the pathogenesis of follicular lymphoma. ..
  13. Aruffo A, Farrington M, Hollenbaugh D, Li X, Milatovich A, Nonoyama S, et al. The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. Cell. 1993;72:291-300 pubmed
    ..The gene encoding gp39 was mapped to Xq26, the X chromosome region where the gene responsible for HIM had previously been mapped. These data suggest that a defect in gp39 is the basis of X-linked HIM. ..
  14. Naim J, Satoh M, Buehner N, Ippolito K, Yoshida H, Nusz D, et al. Induction of hypergammaglobulinemia and macrophage activation by silicone gels and oils in female A.SW mice. Clin Diagn Lab Immunol. 2000;7:366-70 pubmed
    ..These results suggest that silicone gels and oils are capable of inducing hypergammaglobulinemia and activating macrophages in female A.SW mice.
  15. Konstantinopoulos P, Dezube B, Pantanowitz L, Horowitz G, Beckwith B. Protein electrophoresis and immunoglobulin analysis in HIV-infected patients. Am J Clin Pathol. 2007;128:596-603 pubmed
    ..4% had a low-concentration (<5% of total protein) monoclonal band. Hypogammaglobulinemia and polyclonal hypergammaglobulinemia accounted for 1.9% each. In multivariate analysis, younger age (odds ratio [OR], 1...
  16. Leonard A, Meehan S, Ramsey D, Brown L, Sen F. Cutaneous and systemic plasmacytosis. J Am Acad Dermatol. 2007;56:S38-40 pubmed
  17. Chong Y, Ikematsu H, Yamamoto M, Chijiwa K, Ariyama I, Li W, et al. [Effect of highly active antiretroviral therapy (HAART) on hypergammaglobulinemia in HIV infected patients]. Kansenshogaku Zasshi. 2001;75:535-40 pubmed
    To investigate the mechanism of hypergammaglobulinemia in HIV infected patients, the effect of highly active antiretroviral therapy (HAART) on the hypergammaglobulinemia was analyzed...
  18. Tada S, Saito H, Hibi T. [Primary sclerosing cholangitis]. Nihon Rinsho. 2005;63 Suppl 5:501-6 pubmed
  19. Hayes M, Carey J, Krauss J, Hedstrom D, Gulbranson R, Keren D. Low IgE monoclonal gammopathy level in serum highlights 20-yr survival in a case of IgE multiple myeloma. Eur J Haematol. 2007;78:353-7 pubmed
    ..Following chemotherapy, the patient went into clinical remission, eventually dying of complications of emphysema. This case expands the recognized clinical spectrum of IgE multiple myeloma. ..
  20. Granel B, Serratrice J, Disdier P, Sanmarco M, Hubert M, Alessi M, et al. Anti-phospholipid/cofactor antibodies in three cases of persistent polyclonal B lymphocytosis. Br J Haematol. 2002;119:875-6 pubmed
  21. Young T, Jerome D, Gupta S. Hyperimmunoglobulinemia E syndrome associated with coronary artery aneurysms: deficiency of central memory CD4+ T cells and expansion of effector memory CD4+ T cells. Ann Allergy Asthma Immunol. 2007;98:389-92 pubmed
    ..Hyperimmunoglobulinemia E syndrome may be associated with coronary artery aneurysms and with deficiency in CD4+ TEMs and expansion of CD4+ TEMRAs. Comprehensive immunologic evaluation should be performed in patients with this syndrome. ..
  22. Huguet S, Sghiri R, Ballot E, Johanet C. [Analytic study of dot blotting for the detection of anti-Jo-1, anti-M2, anti-ribosomes and anti-LKM]. Ann Biol Clin (Paris). 2004;62:423-9 pubmed
    ..divided into 18 AIH2 and 14 HCV; Group V (n = 22) consisting of 14 healthy individuals and 8 patients with hypergammaglobulinemia. Results of this study are similar to those of Cyto-Dot HM010 for the three auto-antibodies already in use...
  23. Cavazzana I, Franceschini F, Quinzanini M, Manera C, Del Papa N, Maglione W, et al. Anti-Ro/SSA antibodies in rheumatoid arthritis: clinical and immunologic associations. Clin Exp Rheumatol. 2006;24:59-64 pubmed
    ..as xerophthalmia, xerostomia, scleritis, oral ulcers and amyloidosis) and peculiar autoantibody profile (hypergammaglobulinemia, anti-dsDNA and AMA) were found significantly associated to anti-Ro/SSA positivity...
  24. Satoh M, Bjerkås I, Haugarvoll E, Chan E, Szabo N, Jirillo E, et al. Polyclonal hypergammaglobulinemia and autoantibody production induced by vaccination in farmed Atlantic salmon. Fish Shellfish Immunol. 2011;30:1080-6 pubmed publisher
    ..to salmon blood cell (SBC) extract in sera were measured by ELISA and the relationship between hypergammaglobulinemia and autoantibody production was analyzed...
  25. Ramaiah S, Seguin M, Carwile H, Raskin R. Biclonal gammopathy associated with immunoglobulin A in a dog with multiple myeloma. Vet Clin Pathol. 2002;31:83-9 pubmed
    ..To our knowledge, this is the first report of undimerized biclonal gammopathy in a dog caused by a single heavy chain class involving IgA. ..
  26. Brummel R, Lenert P. Activation of marginal zone B cells from lupus mice with type A(D) CpG-oligodeoxynucleotides. J Immunol. 2005;174:2429-34 pubmed
    ..Through increased IL-10 secretion, MZ-B cells may also modify the activity of other cell types, particularly dendritic cells and macrophages...
  27. Brydges S, Kastner D. The systemic autoinflammatory diseases: inborn errors of the innate immune system. Curr Top Microbiol Immunol. 2006;305:127-60 pubmed
    ..In this manuscript, we summarize the current state of the art with regard to the diagnosis, pathogenesis, and treatment of these inborn errors of the innate immune system. ..
  28. Swingler S, Zhou J, Swingler C, Dauphin A, Greenough T, Jolicoeur P, et al. Evidence for a pathogenic determinant in HIV-1 Nef involved in B cell dysfunction in HIV/AIDS. Cell Host Microbe. 2008;4:63-76 pubmed publisher
    B lymphocyte hyperactivation and elevated immunoglobulin levels (hypergammaglobulinemia) are pathogenic manifestations of HIV-1 infection...
  29. Rangel Santos A, Wakim V, Jacob C, Pastorino A, Cunha J, Collanieri A, et al. Molecular characterization of patients with X-linked Hyper-IgM syndrome: description of two novel CD40L mutations. Scand J Immunol. 2009;69:169-73 pubmed publisher
    ..Precise molecular diagnosis in HIGM syndrome allows reliable detection of carriers, making genetic counselling and prenatal diagnosis possible. ..
  30. Kuroda Y, Akaogi J, Nacionales D, Wasdo S, Szabo N, Reeves W, et al. Distinctive patterns of autoimmune response induced by different types of mineral oil. Toxicol Sci. 2004;78:222-8 pubmed
    ..Induction of autoantibodies by mineral oils considered nontoxic also may have pathogenetic implications in human autoimmune diseases. ..
  31. Wang I, Wang S, Yan D, Lin S, Chiang B. Hyper-IgM syndrome: a case report. J Microbiol Immunol Infect. 2003;36:215-7 pubmed
    ..This is the youngest proven case of hyper-IgM syndrome in Taiwan ever reported. ..
  32. Tanko R, Soares A, Müller T, Garrett N, Samsunder N, Abdool Karim Q, et al. Effect of Antiretroviral Therapy on the Memory and Activation Profiles of B Cells in HIV-Infected African Women. J Immunol. 2017;198:1220-1228 pubmed publisher
    ..of effects in B cells, including skewed memory cell differentiation, compromised B cell function, and hypergammaglobulinemia. However, data on the extent to which these B cell abnormalities can be reversed by antiretroviral therapy ..
  33. Soria Valles C, Gutierrez Fernandez A, Osorio F, Carrero D, Ferrando A, Colado E, et al. MMP-25 Metalloprotease Regulates Innate Immune Response through NF-?B Signaling. J Immunol. 2016;197:296-302 pubmed publisher
    ..mice exhibit a defective innate immune response characterized by low sensitivity to bacterial LPS, hypergammaglobulinemia, and reduced secretion of proinflammatory molecules...
  34. Schubach T, Schubach A, Okamoto T, Barros M, Figueiredo F, Cuzzi T, et al. Canine sporotrichosis in Rio de Janeiro, Brazil: clinical presentation, laboratory diagnosis and therapeutic response in 44 cases (1998-2003). Med Mycol. 2006;44:87-92 pubmed
    ..8%) were cured after treatment, and two (6%) continue to be treated. The present cases indicate that many dogs with sporotrichosis respond well to treatment and in a few dogs, the disease may be self-limiting. ..
  35. Malladi A, Sack K, Shiboski S, Shiboski C, Baer A, Banushree R, et al. Primary Sjögren's syndrome as a systemic disease: a study of participants enrolled in an international Sjögren's syndrome registry. Arthritis Care Res (Hoboken). 2012;64:911-8 pubmed publisher
    ..Laboratory abnormalities, including hematologic abnormalities, hypergammaglobulinemia, and hypocomplementemia, frequently occurred among primary SS cases and were more common among the ..
  36. DeMarchi J, Papasidero S, Medina M, Klajn D, Chaparro Del Moral R, Rillo O, et al. Primary Sjögren's syndrome: Extraglandular manifestations and hydroxychloroquine therapy. Clin Rheumatol. 2017;36:2455-2460 pubmed publisher
    ..001), fatigue (p < 0.001), purpura (p = 0.01), Raynaud phenomenon (p = 0.003), and hypergammaglobulinemia (p = 0.006). Immunosuppressive treatment was indicated on 28 patients (12...
  37. Ma Z, Xie Y, Wang Y, Ma L, He Y, Zhang Y, et al. [Peripheral blood CD4?;CXCR5?; follicular helper T cells are related to hyperglobulinemia of patients with chronic hepatitis B]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2013;29:515-8, 521 pubmed
    ..05). The results suggest that CD4?;CXCR5?;Tfh cells may participate in the pathogenesis of hyperglobulinemia during HBV infection. ..
  38. Mijuşković Z, Zecevic R, Pavlovic M. Pyoderma gangrenosum with spleen involvement and monoclonal IgA gammopathy. J Eur Acad Dermatol Venereol. 2004;18:697-9 pubmed
    ..Systemic involvement in pyoderma gangrenosum is very rare, and according to our knowledge there are only a few cases with spleen involvement. ..
  39. Marchetti F, Barbi E, Tommasini A, Oretti C, Ventura A. Inefficacy of etanercept in a child with hyper-IgD syndrome and periodic fever. Clin Exp Rheumatol. 2004;22:791-2 pubmed
  40. Mathieu P, Gómez K, Coutelier J, Retegui L. Identification of two liver proteins recognized by autoantibodies elicited in mice infected with mouse hepatitis virus A59. Eur J Immunol. 2001;31:1447-55 pubmed
    ..No correlation was found between the development of the hypergammaglobulinemia that followed the viral infection and the occurrence of the autoAb...
  41. Schmoll F, Sipos W, Kahlbacher H, Schilcher F, Bago Z, Bunka S, et al. Clinical and pathological features of the Porcine Ulcerative Dermatitis Syndrome (PUDS). J Vet Med A Physiol Pathol Clin Med. 2004;51:15-8 pubmed
    ..This supports the hypothesis that not only T cells, as shown previously, but also the humoral branch of the immune system is involved in the aetiology of PUDS. ..
  42. Liu W, Szalai A, Zhao L, Liu D, Martin F, Kimberly R, et al. Control of spontaneous B lymphocyte autoimmunity with adenovirus-encoded soluble TACI. Arthritis Rheum. 2004;50:1884-96 pubmed
    ..in the absence of severe disease, treatment of younger mice with AdTACI prevented the development of hypergammaglobulinemia. In contrast, use of AdTACI for BLyS blockade had only transient effects on the levels of IgG in normal B6 ..
  43. Fiorini C, Jilani S, Losi C, Silini A, Giliani S, Ferrari S, et al. A novel activation-induced cytidine deaminase gene mutation in a Tunisian family with hyper IgM syndrome. Eur J Pediatr. 2004;163:704-8 pubmed
    ..This alteration leads to the use of two cryptic splicing sites causing the formation of two different mRNA species. ..
  44. Andrew N, Kearney D, Selva D. IgG4-related orbital disease: a meta-analysis and review. Acta Ophthalmol. 2013;91:694-700 pubmed publisher
    ..Its pathogenesis may involve an immune response to antigen exposure in the upper aerodigestive tract. ..
  45. Nonoyama S. [Hyper IgM syndrome]. Nihon Rinsho Meneki Gakkai Kaishi. 2002;25:123-5 pubmed
  46. Wu C, Li R, Qi L, Xia D. [Clinical analysis of 126 children with hemorrhagic fever with renal syndrome]. Zhonghua Er Ke Za Zhi. 2003;41:703-4 pubmed
  47. Himi T, Takano K, Yamamoto M, Naishiro Y, Takahashi H. A novel concept of Mikulicz's disease as IgG4-related disease. Auris Nasus Larynx. 2012;39:9-17 pubmed publisher
    ..MD and KT differ from SS and are thought to be singular systemic IgG4-related plasmacytic diseases. Here we discuss the results of recent studies and provide an overview of MD as an IgG4-related disease. ..
  48. Garside J, Kerrin D, Brownlee K, Gooi H, Taylor J, Conway S. Immunoglobulin and IgG subclass levels in a regional pediatric cystic fibrosis clinic. Pediatr Pulmonol. 2005;39:135-40 pubmed
    ..Eleven patients had hypergammaglobulinemia (7.8% compared with 0-69% in the published literature)...
  49. Groeneweg M, Lankester A, Bredius R. [From gene to disease; CD40 ligand deficiency as the cause of X-linked hyper-IgM-syndrome]. Ned Tijdschr Geneeskd. 2003;147:1009-11 pubmed
    ..Patients with XHIM present with severe, recurrent infections, predominantly of the respiratory and gastrointestinal tract. The gene encoding the CD40 ligand is located on the long arm of the X chromosome. ..
  50. Escárcega Barbosa D, Ortiz Jiménez M, Juárez García J, Miranda Feria A. [Hyper-IgM syndrome: mucocutaneous lesions and neutropenia]. Rev Alerg Mex. 2002;49:57-9 pubmed
    ..Intravenous immune globulin improves dramatically the disorder, including neutropenia. To date, periodical infusion of immune globulin has prevented the development of serious infections. ..
  51. Melikyan A, Egorova E, Julhakyan H, Kovrigina A, Savchenko V. Human Herpesvirus Type 8-positive Multicentric Castleman Disease. Clin Lymphoma Myeloma Leuk. 2016;16 Suppl:S159-65 pubmed publisher
    ..Various laboratory changes were observed, but the most significant were anemia, thrombocytopenia, hypergammaglobulinemia, M-component, increased erythrocyte sedimentation rate, and circulating immune complexes...
  52. Chong Y, Ikematsu H, Ariyama I, Chijiwa K, Li W, Yamaji K, et al. Evidence of B cell clonal expansion in HIV type 1-infected patients. AIDS Res Hum Retroviruses. 2001;17:1507-15 pubmed
    ..we examined the expressed V(H)DJ(H) gene sequences of peripheral B cells in HIV-1-infected patients with hypergammaglobulinemia. Identical V(H)DJ(H) gene rearrangements with additional nucleotide differences in V(H) genes were ..
  53. Moschese V, Lintzman J, Callea F, Chini L, Devito R, Carsetti R, et al. A novel form of non-X-linked hyperigm associated with growth and pubertal disturbances and with lymphoma development. J Pediatr. 2006;148:404-6 pubmed
    ..We report on two female patients affected by a novel syndrome associating HIGM, growth and pubertal disturbances, and severe lymphoid hyperplasia with eventual development into lymphomas, suggesting a DNA repair defect. ..