heavy chain disease


Summary: A disorder of immunoglobulin synthesis in which large quantities of abnormal heavy chains are excreted in the urine. The amino acid sequences of the N-(amino-) terminal regions of these chains are normal, but they have a deletion extending from part of the variable domain through the first domain of the constant region, so that they cannot form cross-links to the light chains. The defect arises through faulty coupling of the variable (V) and constant (C) region genes.

Top Publications

  1. Husby G. Is there a pathogenic link between gamma heavy chain disease and chronic arthritis?. Curr Opin Rheumatol. 2000;12:65-70 pubmed
    In 1991, gamma heavy chain disease was diagnosed in a 43-year-old female, who 3 years earlier had contracted an erosive seronegative chronic arthropathy...
  2. Wahner Roedler D, Witzig T, Loehrer L, Kyle R. Gamma-heavy chain disease: review of 23 cases. Medicine (Baltimore). 2003;82:236-50 pubmed
    We report the cases of 23 patients with gamma-heavy chain disease seen at our institution (8 patients previously reported, 15 new patients). There were 15 women and 8 men; the median age at diagnosis was 68 years (range, 42-87 yr)...
  3. Fermand J, Brouet J, Danon F, Seligmann M. Gamma heavy chain "disease": heterogeneity of the clinicopathologic features. Report of 16 cases and review of the literature. Medicine (Baltimore). 1989;68:321-35 pubmed
    ..This review underscores the diversity of the clinical manifestations and hematopathological features of gamma heavy chain disease based on the detailed report of 16 patients evaluated in our chemical department, the analysis of 12 cases ..
  4. Morita K, Kawamoto H, Takada H, Nakamura S, Ishii K, Okamoto Y. Unusual gamma heavy chain disease protein in a patient with splenic marginal-zone lymphoma. Ann Clin Biochem. 2006;43:161-4 pubmed
    ..serum immunoglobulin composed of only gamma heavy chain has been known as a fundamental feature of gamma heavy chain disease (HCD)...
  5. Lee M, Parwani A, Humphrey R, Hamilton R, Myers D, Detrick B. Gamma heavy chain disease in a patient with diabetes and chronic renal insufficiency: diagnostic assessment of the heavy chain fragment. J Clin Lab Anal. 2008;22:146-50 pubmed publisher
    ..In conclusion, we portray a patient with an underlying monoclonal gamma heavy chain disease (HCD) who presented with a complex medical history...
  6. Fermand J, Brouet J. Heavy-chain diseases. Hematol Oncol Clin North Am. 1999;13:1281-94 pubmed
    ..Cells producing HCD may, however, all derive from a common normal precursor, which could be a rare B cell in the process of immunoglobulin gene somatic mutation within the germinal center...
  7. Luraschi P, Infusino I, Zorzoli I, Merlini G, Fundarò And C, Franzini C. Heavy chain disease can be detected by capillary zone electrophoresis. Clin Chem. 2005;51:247-9 pubmed
  8. Wahner Roedler D, Kyle R. Heavy chain diseases. Best Pract Res Clin Haematol. 2005;18:729-46 pubmed
    ..Prognosis is variable, and no standardized effective treatment programs are available except for alpha-HCD, which in its early stage may respond to antibiotics. ..
  9. Munshi N, Digumarthy S, Rahemtullah A. Case records of the Massachusetts General Hospital. Case 13-2008. A 46-year-old man with rheumatoid arthritis and lymphadenopathy. N Engl J Med. 2008;358:1838-48 pubmed publisher

More Information


  1. Mariën G, Verhoef G, Bossuyt X. Detection of heavy chain disease by capillary zone electrophoresis. Clin Chem. 2005;51:1302-3 pubmed
  2. Johannis W, Blommer J, Klatt A, Renno J, Wielckens K. Gamma heavy chain disease in a patient with rheumatoid arthritis--a laboratory evaluation. Biochem Med (Zagreb). 2012;22:373-9 pubmed
    ..rare and probably underdiagnosed diseases the aim of this report is to show an additional case of gamma heavy chain disease in a 48 year old female patient with rheumatoid arthritis focusing on the laboratory presentation...
  3. Cheng I, Ho S, Chan D, Ng W, Chan K. Crescentic nodular glomerulosclerosis secondary to truncated immunoglobulin alpha heavy chain deposition. Am J Kidney Dis. 1996;28:283-8 pubmed
  4. Fakhfakh F, Dellagi K, Ayadi H, Bouguerra A, Fourati R, Ben Ayed F, et al. Alpha heavy chain disease alpha mRNA contain nucleotide sequences of unknown origins. Eur J Immunol. 1992;22:3037-40 pubmed
    Human alpha heavy chain disease is characterized by the production of abnormally short alpha IgH chains...
  5. Cogne M, Bakhshi A, Korsmeyer S, Guglielmi P. Gene mutations and alternate RNA splicing result in truncated Ig L chains in human gamma H chain disease. J Immunol. 1988;141:1738-44 pubmed
    ..RIV leukemic cells as well as myeloma cells transfected with the RIV kappa gene synthesized a truncated protein. Simultaneous defects in H and L chains genes may reflect a hypermutational mechanism for Ig genes in B cells. ..
  6. Garcia Munoz R, Panizo E, Rodriguez Otero P, Mugueta Uriaque M, Rifon J, Llorente L, et al. Systemic lupus erythematosus and Franklin's disease: when the somatic mutation mechanism makes a mistake. Rheumatology (Oxford). 2008;47:1105-6 pubmed publisher
  7. Herzenberg A, Kiaii M, Magil A. Heavy chain deposition disease: recurrence in a renal transplant and report of IgG(2) subtype. Am J Kidney Dis. 2000;35:E25 pubmed
    ..Neither patient had myeloma. The complete spectrum of gamma-HCDD subtypes has now been reported. Further data are required to make conclusive statements about the true recurrence rate of HCDD in renal transplants. ..
  8. Takatani T, Morita K, Takaoka N, Tatsumi M, Okuno Y, Masutani T, et al. Gamma heavy chain disease screening showing a discrepancy between electrophoretic and nephelometric determinations of serum gamma globulin concentration. Ann Clin Biochem. 2002;39:531-3 pubmed
    ..Thus, the patient was diagnosed with gamma heavy chain disease. A comparison of gamma globulin levels determined by different methods may be useful when screening for ..
  9. Sakakima M, Fujigaki Y, Tsuji T, Fukasawa H, Miyaji T, Naito K, et al. High dose chemotherapy and stem cell support in a patient of light- and heavy-chain deposition disease with abnormal marrow cell surface antigens and no monoclonal protein. Intern Med. 2005;44:970-4 pubmed
    ..Immunophenotypic analysis of marrow cells facilitates clinical decision making regarding the use of HDC/PBSCT for LHCDD patients without monoclonal protein. ..
  10. Gallo G, Picken M, Frangione B, Buxbaum J. Nonamyloidotic monoclonal immunoglobulin deposits lack amyloid P component. Mod Pathol. 1988;1:453-6 pubmed
  11. Cogne M, Aucouturier P, Brizard A, Dreyfus B, Duarte F, Preud homme J. Complete variable region deletion in a mu heavy chain disease protein (ROUL). Correlation with light chain secretion. Leuk Res. 1993;17:527-32 pubmed
  12. Price S. Immunoproliferative small intestinal disease: a study of 13 cases with alpha heavy-chain disease. Histopathology. 1990;17:7-17 pubmed
    ..It is concluded that IPSID with alpha-heavy-chain disease is neoplastic in all its stages and is a variant of mucosa-associated lymphoma. The role of centrocyte-like cells and the response to conservative therapy are discussed...
  13. Tubbs R, Berkley V, Valenzuela R, McMahon J, Gephardt G, Fishleder A, et al. Pseudo-gamma heavy chain (IgG4 lambda) deposition disease. Mod Pathol. 1992;5:185-90 pubmed
    ..Neither circulating (peripheral blood and bone marrow serum) nor cellular free gamma chains were present. We propose the term "pseudo-gamma heavy chain deposition disease" for the process. ..
  14. Tichy M, Stulik J, Osanec J, Skopek P. Electrophoretic characterization of a gamma-1-heavy chain disease. Neoplasma. 2000;47:118-21 pubmed
    This report describes a new case of gamma-1-heavy chain disease found in a woman with malignant lymphoproliferative disease...
  15. Thompson K, Sletten K, Brandtzaeg P, Källberg E, Wien T, Husby G. Articular, monoclonal gamma3 heavy-chain deposition disease: characterization of a partially deleted heavy-chain gene and its protein product synthesized in vivo and in vitro. Arthritis Rheum. 2003;48:3266-71 pubmed
    ..To our knowledge, this is the first reported case of gammaHCDD causing an erosive, polyarticular arthropathy as the dominating clinical feature. ..
  16. Sharma O. Paraproteinemias and the lungs. Curr Opin Pulm Med. 2005;11:408-11 pubmed
  17. Demeule B, Gurny R, Arvinte T. Where disease pathogenesis meets protein formulation: renal deposition of immunoglobulin aggregates. Eur J Pharm Biopharm. 2006;62:121-30 pubmed
    ..If the formulation provides a slightly destabilizing environment to the protein, the long-term stability of the drug may be compromised by aggregate formation. ..
  18. Inoue D, Matsushita A, Kiuchi M, Takiuchi Y, Nagano S, Arima H, et al. Successful treatment of ?-heavy-chain disease with rituximab and fludarabine. Acta Haematol. 2012;128:139-43 pubmed
    ..This report suggests the efficacy of rituximab plus fludarabine therapy for LPL-associated ?-HCD. ..
  19. Mitchell P, Ford R, Coughtrie M, Heppleston A, Fraser C. A case of heavy chain disease: diagnosis and monitoring using assays of immunoglobulin heavy and light chains. Scott Med J. 1990;35:18-9 pubmed
    ..Heavy chain diseases (HCD) are uncommon. We report the first use of recently developed analytical techniques for the assay of immunoglobulin heavy and light chains in the diagnosis and monitoring of a patient with gamma-HCD. ..
  20. Hill J, Mulligan G. Subepithelial corneal deposits in IgG lambda myeloma. Br J Ophthalmol. 1989;73:552-4 pubmed
    ..Electrophoretic studies showed that the deposits consisted of an IgG lambda paraprotein identical to that found in the serum. Minute amounts of the papaprotein were also present in the tears. ..
  21. Itoh Y. [Laboratory investigation on M-protein and its clinical application. 1. Introduction]. Rinsho Byori. 2001;49:675-7 pubmed
    ..The paper outlines a routine-based laboratory approach on monoclonal protein in relevance with its classification, laboratory methods and the related diseases, thus giving general orientations for the paper followed. ..
  22. Tan J, Kroll M, O Hara C, Everett P, Erdogan E. Gamma heavy chain disease in a patient with underlying lymphoplasmacytic lymphoma of the thyroid. Report of a case and comparison with other reported cases with thyroid involvement. Clin Chim Acta. 2012;413:1696-9 pubmed publisher
    Gamma heavy chain disease with underlying thyroid pathology is rare...
  23. Suzuki K. Light- and heavy-chain deposition disease (LHCDD): difficulty in diagnosis and treatment. Intern Med. 2005;44:915-6 pubmed
  24. Soma J, Tsuchiya Y, Sakuma T, Sato H. Clinical remission and histopathological resolution of nodular lesions in a patient with gamma3 heavy-chain deposition disease. Clin Nephrol. 2008;69:383-6 pubmed
    ..This is the first case report to indicate that the original structure of glomeruli in patients with HCDD could be restored within a few years by an appropriate treatment at an early stage of the disease. ..
  25. Ieko M, Kohno M, Ohmoto A, Notoya A, Fukazawa Y, Yasukouchi T, et al. [Gamma-heavy chain disease associated with MALT lymphoma of the duodenum]. Rinsho Ketsueki. 1998;39:512-8 pubmed
    We report a case of a 63-year-old woman with gamma heavy chain disease (HCD) associated with mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum. She was suffering from drug-resistant tonsillitis with high fever...
  26. Oe Y, Nakaya I, Yahata M, Sakuma T, Sato H, Soma J. A case of ?1-heavy chain deposition disease successfully treated with melphalan and prednisolone therapy. Intern Med. 2010;49:1411-5 pubmed
    ..Although renal prognosis of HCDD is poor, aggressive chemotherapy with MP may be effective in early-stage HCDD patients. ..
  27. Castelino D, Gray F, d Apice A, Paspaliaris B, Riglar A, McLachlan R, et al. Primary Sjögren's syndrome and gamma heavy chain disease. Pathology. 1994;26:337-8 pubmed
    We describe a patient who has primary Sjögren's syndrome associated with asymptomatic gamma heavy chain disease and a tubulointerstitial nephritis...
  28. Seligmann M. [Heavy chain diseases]. Rev Prat. 1993;43:317-20 pubmed
    ..At the terminal stage, a malignant lymphoma, often of immunoblastic type, occurs. The natural history and epidemiology of alpha HCD should provide insights into the pathogenesis of malignant lymphoid proliferations. ..
  29. Iwasaki T, Hamano T, Kobayashi K, Kakishita E. A case of mu-heavy chain disease: combined features of mu-chain disease and macroglobulinemia. Int J Hematol. 1997;66:359-65 pubmed
    A case of mu-heavy chain disease (HCD) is described. The patient, a 40-year-old man, presented with an intracranial tumor. The bone marrow of this patient showed infiltration with both plasma cells and lymphocytes...
  30. Yunokawa K, Hagiyama Y, Mochizuki Y, Tanaka N, Ochi M. Hypertrophic spinal pachymeningitis associated with heavy-chain disease. Case report. J Neurosurg Spine. 2007;7:459-62 pubmed
    ..Idiopathic HSP may be secondary to rare conditions such as HCD, and systemic examinations should be performed to the fullest extent possible to investigate the possibility of some underlying disease. ..
  31. Kanoh T, Takigawa M, Niwa Y. Cutaneous lesions in gamma heavy-chain disease. Arch Dermatol. 1988;124:1538-40 pubmed
    ..Erythematous, infiltrated plaques and extensive, heavy pleomorphic lymphoid cell infiltrates of the dermis were observed in a patient with gamma heavy-chain disease. ..
  32. Pellet P, Berger R, Bernheim A, Brouet J, Tsapis A. Molecular analysis of a t(9;14)(p11;q32) translocation occurring in a case of human alpha heavy chain disease. Oncogene. 1989;4:653-7 pubmed
    ..This t(9;14)(p11;q32) translocation was found in a case of malignant lymphoma occurring in human alpha heavy chain disease. A rearranged alpha 1 gene fragment was cloned and shown to contain chromosome 9 information by Southern ..
  33. Fakhfakh F, Mihaesco E, Ayadi H, Brouet J, Tsapis A. [Alpha heavy chain disease. Molecular analysis of a new case]. Presse Med. 1993;22:1047-51 pubmed
    ..abnormal protein, as well as the sequence of the corresponding mRNA, were determined in a new case of alpha heavy chain disease. The patient presented with typical clinical features of the disease...
  34. Buxbaum J. Abnormal immunoglobulin synthesis in monoclonal immunoglobulin light chain and light and heavy chain deposition disease. Amyloid. 2001;8:84-93 pubmed
    ..In either case the fragments may be more susceptible to tissue deposition, with subsequent organ compromise, than intact Ig chains. ..
  35. Vignon M, Cohen C, Faguer S, Noel L, Guilbeau C, Rabant M, et al. The clinicopathologic characteristics of kidney diseases related to monotypic IgA deposits. Kidney Int. 2017;91:720-728 pubmed publisher
    ..Clinicopathologic characteristics of ?-heavy chain deposition disease resemble those of the ?-heavy chain disease, except for a higher frequency of extra-capillary proliferation and extra-renal involvement...
  36. Kyle R. Clinical aspects of multiple myeloma and related disorders including amyloidosis. Pathol Biol (Paris). 1999;47:148-57 pubmed
    ..The subcutaneous fat aspirate is positive in 80% while the bone marrow is positive in 55%. If these tissues are negative, one should obtain tissue from an involved organ. ..
  37. Orth H, Hurwitz N, Lohri A, Weber W, Herrmann R. [gamma-heavy chain production as an epiphenomenon in non-Hodgkin's lymphoma]. Dtsch Med Wochenschr. 1994;119:1235-8 pubmed
    ..The gamma heavy chain production added little to the histomorphological characterization of the underlying lymphoma, as well as its treatment and prognosis. ..
  38. Danevad M, Sletten K, Gaarder P, Mellbye O, Husby G. The amino acid sequence of a monoclonal gamma 3-heavy chain from a patient with articular gamma-heavy chain deposition disease. Scand J Immunol. 2000;51:602-6 pubmed
  39. Witzig T, Wahner Roedler D. Heavy chain disease. Curr Treat Options Oncol. 2002;3:247-54 pubmed
    ..Patients with MGUS with NHL should be administered chemotherapy. Screening the serum and urine of patients with lymphoplasmacytoid NHL would likely identify more patients with gamma- or mu-HCD. ..
  40. Husby G, Blichfeldt P, Brinch L, Brandtzaeg P, Mellbye O, Sletten K, et al. Chronic arthritis and gamma heavy chain disease: coincidence or pathogenic link?. Scand J Rheumatol. 1998;27:257-64 pubmed
    In 1991, gamma heavy chain disease was diagnosed in a 43-year-old female, who 3 years earlier had contracted an erosive seronegative chronic arthropathy...
  41. Safa G, Dhib M, Soubrane J, Thomine E, Delpech A, Francois A, et al. [Light and heavy chain deposition disease with cutaneous and renal manifestations]. Ann Dermatol Venereol. 1996;123:490-2 pubmed
  42. Tissot J, Schneider P. [Two-dimensional electrophoretic study of monoclonal gammopathies and cold agglutinins associated with a chronic hemolytic anemia]. Rev Fr Transfus Hemobiol. 1989;32:345-56 pubmed
    ..We think that the 2-DGE is a very usefull specialized aid to the analysis of such particular immunohematological problems. ..
  43. Yazaki M, Fushimi T, Tokuda T, Kametani F, Yamamoto K, Matsuda M, et al. A patient with severe renal amyloidosis associated with an immunoglobulin gamma-heavy chain fragment. Am J Kidney Dis. 2004;43:e23-8 pubmed
    ..Microextraction and biochemical characterization of amyloid fibrils was of great use for reaching a definitive diagnosis. ..
  44. Tungekar M, Omar Y, Behbehani K. Gastric alpha heavy chain disease. Oncology. 1987;44:360-6 pubmed
    Clinicopathological and immunohistological features of 4 cases of gastric lymphomas with alpha-heavy chain disease (AHCD) are described...
  45. Alexander M, Nasr S, Watson D, Mendez G, Rennke H. Renal crescentic alpha heavy chain deposition disease: a report of 3 cases and review of the literature. Am J Kidney Dis. 2011;58:621-5 pubmed publisher
    ..In this report, we describe 3 additional cases of ? HCDD, all with a crescentic pattern of injury and one of which was associated with cutis laxa. We compare their clinicopathologic features with all previously reported cases of HCDD. ..
  46. Wahner Roedler D, Kyle R. Mu-heavy chain disease: presentation as a benign monoclonal gammopathy. Am J Hematol. 1992;40:56-60 pubmed
    mu-Heavy chain disease (HCD) is a rare monoclonal lymphoid disorder characterized by the failure to assemble a complete IgM immunoglobulin...
  47. Tan S, Pon K, Bargman J, Ghazarian D. Generalized cutis laxa associated with heavy chain deposition disease. J Cutan Med Surg. 2003;7:390-4 pubmed
    ..On pathology, there was destruction of elastic fibers within the dermis. This case describes a previously unreported association between acquired cutis laxa and heavy chain deposition disease. ..
  48. Hudnall S, Alperin J, Petersen J. Composite nodular lymphocyte-predominance Hodgkin disease and gamma-heavy-chain disease: a case report and review of the literature. Arch Pathol Lab Med. 2001;125:803-7 pubmed
    ..Given recent data indicating the B-cell nature of this form of Hodgkin disease, the authors propose that in this unique case there may be a clonal relationship between these 2 concurrent B-cell lymphoproliferative processes. ..
  49. Brioli A, Zamagni E, Pasquali S, Tosi P, Tacchetti P, Perrone G, et al. Long-term follow-up after autologous stem cell transplantation for light- and heavy-chain deposition disease. Bone Marrow Transplant. 2012;47:1248-9 pubmed publisher
  50. Presti B, Sciotto C, Marsh S. Lymphocytic lymphoma with associated gamma heavy chain and IgM-lambda paraproteins. An unusual biclonal gammopathy. Am J Clin Pathol. 1990;93:137-41 pubmed
    ..Levels of the two paraproteins were unaltered by surgical excision of the colonic carcinoma but were reduced by chemotherapy directed at the lymphoma. ..
  51. Leloup E, Gallinari C, Bouchon J, Benis Y. [Heavy gamma-chain diseases. A new case and review of the literature]. Ann Med Interne (Paris). 1989;140:274-8 pubmed
    IgG heavy chain disease is a rare disorder in which incomplete monoclonal immunoglobulins are synthesized...
  52. Di Benedetto G, Cataldi A, Verde A, Gloghini A, Nicolo G, Pistoia V. Gamma heavy chain disease associated with Hodgkin's disease. Clinical, pathologic, and immunologic features of one case. Cancer. 1989;63:1804-9 pubmed
    This report describes the clinical, pathologic, and immunologic features of a patient with gamma heavy chain disease (gamma-HCD) associated with Hodgkin's disease (HD)...
  53. Pellet P, Hillion J, Carroll A, Crist W, Brouet J, Tsapis A. Heterogeneity of the breakpoint localization in malignant cells with a 9p11 chromosomal abnormality. Leukemia. 1991;5:468-72 pubmed
    ..Using pulsed-field electrophoresis analysis we demonstrated that the breakpoints were 3-300 kb distant from the original MAL breakpoint without clustering within the subset of leukemias with the tdic(9;12). ..