The "cure" of an inherited disease
Alper, C.A.
Journal of Laboratory and Clinical Medicine 92(4): 497-500
1978
ISSN/ISBN: 0022-2143 PMID: 712188 Document Number: 133682
Although the disease is rare, it can be surmised that a significant proportion of affected families in this country have been identified. Well over 100 apparently unrelated kindred are known. It is only in the last 2 decades, with characterization of proteins and reaction mechanisms within the complement, fibrinolytic, coagulation and kinin systems, that insight was obtained into the molecular basis of HANE. As mentioned earlier, the molecular basis of HANE is a deficiency of C.hivin.1 inhibitor activity. In about 85% of families, the protein is present in subnormal amounts, and in the remaining affected kindred, C.hivin.1 inhibitor protein levels are normal or even supranormal but the protein does not function normally. Among the unrelated patients with dysfunctional mutant proteins, at least 4 different mutations can be detected by the electrophoretic mobility and serum concentration of the gene products. Almost 20 yr ago about half of the patients with HANE responded to oral methyltestosterone with a complete disappearance of symptoms. More recently, synthetic androgens, including the impeded androgen danazol (impeded androgens have anabolic but little masculinizing activity), have been found to induce complete remission in almost all patients with HANE. Even more remarkably, patients with deficient C.hivin.1 inhibitor receiving danazol sustain a rise in C.hivin.1 inhibitor to normal or near-normal serum levels and a rise to normal of C4 and C2 concentrations. In patients with dysfunctional protein, normal C.hivin.1 inhibitor appears and ultimately is equal in concentration to dysfunctional inhibitor. If the latter was in supranormal concentration, it falls toward normal.