Heavy-chain disease

The heavy-chain diseases (HCDs) are monoclonal lymphoplasma cell proliferative disorders involving B cells and are characterized by the synthesis of truncated heavy chains without associated light chains. The complex abnormalities of HCD proteins and the usual lack of normal light chains are due to several distinct gene alterations, including somatic mutations, deletions, and insertions. HCDs have been described for the three main immunoglobulin classes. The most frequent is α-HCD; μ-HCD is rare and the incidence of γ-HCD is intermediate. In contrast to γ-HCD and α-HCD, which usually have no detectable monoclonal light chains, the light chains that do not assemble with the secreted deleted heavy chains are produced in about two-thirds of cases of μ-HCD. The monoclonal proteins are always present in the serum and are often in the urine of patients with γ-HCD, but monoclonal heavy chains are infrequent in the urine in μ-HCD and occur in small amounts in α-HCD.