Mu Heavy Chain Disease
- Author: Ajeet Gajra, MD; Chief Editor: Emmanuel C Besa, MD more...
Heavy chain diseases (HCDs) are rare B-cell proliferative disorders characterized by the synthesis and secretion of incomplete immunoglobulin heavy chains. These disorders initially were recognized as gammopathies due to the presence of monoclonal proteins in the patient's serum or urine. The disorders were defined in terms of the production of structurally aberrant immunoglobulin molecules.
Normal immunoglobulin molecules are symmetrical and are composed of 2 pairs of polypeptide chains designated the light and heavy chains, which are interconnected by disulfide bonds. The heavy chains are the larger polypeptide subunits; they are specific and distinctive structures that distinguish the major classes of immunoglobulins. Reductive cleavage of the immunoglobulin molecule by papain yields 2 Fab fragments (consisting of a light chain and an Fd fragment) and one Fc fragment (consisting of portions of the 2 heavy chains).
Plasma cell disorders characterized by an anomalous serum and urinary protein that is immunochemically related to the Fc fragment of the immunoglobulin molecule are known as HCDs. When the anomalous protein structurally resembles the heavy chain fragment of immunoglobulin M (IgM) molecule, it is designated as mu-HCD. Ballard and colleagues first described this entity in 1970.
This article focuses on mu-HCD; however, other heavy chain diseases are described (eg, see Heavy Chain Disease, Gamma).
Mu heavy chain disease was first described in 1969. The characteristic feature of HCD is the production of a monoclonal immunoglobulin molecule in which the heavy chain is truncated and the covalent attachment of light chains is absent. This may be due to lack of light chain production or the failure of heavy-light disulfide bond formation.
The mu heavy chains analyzed to date have an absent variable region and a shortened constant domain. The reasons a complete immunoglobulin fails to assemble are poorly understood. A defect at the level of immunoglobulin gene structure and assembly has been shown to be responsible for the synthesis of the truncated mu-HCD protein, caused by deletion of coding information and formation of an aberrant RNA molecule. The available data do not allow for an accurate description of the molecular defects involved in mu-HCD proteins. Despite certain similarities, every case seems to have an individual pattern.[4, 5]
Mu heavy chain disease is rare, with 34 cases reported in the literature. However, many cases likely have not been reported, especially in the past decade. Given the difficulty in diagnosing this disorder, most reports are from the United States, Western Europe, and Scandinavia.
True international incidence is difficult to ascertain for reasons stated above. A single case has been reported from Japan.
Given its infrequent presentation, mu-HCD is not a major cause of morbidity or mortality. The disease course can be extremely variable, and the survival of patients in the literature reports varies from 1 month to 11 years. Reports of cures are also described.
Race-, Sex-, and Age-related Demographics
Most patients with mu-HCD reported in the literature were white, but at least three black patients and one Asian patient have also been reported. No obvious sex predilection has been described. Nor does mu-HCD have an obvious age predilection; the age of reported patients has ranged from 15-80 years.
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