A group of three rare B cell neoplasms associated with abnormal immunoglobulin heavy chains incapable of binding light chains.
Abnormal heavy chains contain deletions, insertions, and point mutations acquired during somatic hypermutations.
The above alterations result in a loss of a large part of the constant-1 (CH 1) domain of the immunoglobulin heavy chain molecule responsible for light chain binding, with variable effects on the variable (V), diversity (D) , and joining (J) regions.
When the CH1 domain of a normal heavy chain is not associated with the light chain it binds to heat-shock protein 78 and undergoes degradation in the proteosome of the cell.
Normal heavy chains unassociated with light chains are not detected in serum or urine.
In heavy chain diseases changes in the CH1 domain prevents the heavy chain from binding both to the light chain and heat-shock protein 78, allowing it to bypass degradation by the proteasome and be secreted into the serum or urine.
Abnormal heavy chains form part of the transmembrane B-cell receptor and may facilitate antigenic independent aggregation and downstream signaling by the receptor, conf2242ing growth of neoplastic cells.
Heavy chain diseases represent an unusual variant of a type of lymphoma and are not plasma cell neoplasms.
Alpha heavy chain disease is the most common of the heavy chain diseases.
Most commonly affects individuals of Medit2242anean, North-African, and Middle Eastern descent.
More common among members of the lower socioeconomic group, suggesting an environmental and or possibly infectious process.
Has a slight male predominance.
Most prevalent during the second and third decades of life.
Alpha heavy chain disease primarily affects the gastrointestinal tract with rare involvement of the respiratorytract and lymphoma type forms.
The G.I. form presents as a malabsorption syndrome manifesting with weight loss, diarrhea, and abdominal discomfort, and nausea and emesis may occur.
The digestive form of Alpha heavy chain disease may manifest with as cites and anasarca.
Generalized lymph node enlargement and splenomegaly may be present in the gastrointestinal form, but are common in the lymphomatosis form.
The respiratory form of Alpha heavy chain disease maybe associated with hypoxemia, dyspnea and pulmonary infiltrates with restrictive pulmonary function tests.
Hilar adenopathy and lymphomatous involvement of the pharyngeal mucosa, skin rash and eosinophilia have also been reported.