Serum putrescine (Pu), spermidine (Sd), spermine (Sp), and plasma diamine oxidase activity (DAO) were determined in cystic fibrosis (CF) homozygotes and heterozygotes plus age-matched controls. Mean (±S.E.) levels of Pu (0.51 ± 0.06 nmoles/ml), Sd (0.63 ± 0.07nmoles/ml), and Sp (0.33 ± 0.08 nmoles/ml) were higher (P < 0.001) in 17 control children versus 16 healthy adults (Pu = 0.15 ± 0.04; Sd = 0.14 ± 0.03; Sp = 0 in all). All 4 CF adults tested, but only 3 of 24 CF children, had increased poly- amines relative to age-matched controls. Pu (0.33 ± 0.04), Sd (0.33 ± 0.05) and Sp (0.16 ± 0.12) were increased (P < 0.001) in 11 adult heterozygotes; in turn, Pu (0.56 ± 0.11; P < 0.025) and Sd (0.86 ± 0.22; P < 0.005) were higher in the adult CF patients than in the heterozygotes. Plasma DAO was higher (P < 0.001) in 45 control children (9.3 ± 0.7 units/ml) versus 61 healthy adults (5.7 ± 0.07). Levels > +2 S.D. for controls occurred in 8 (21%) of 39 CF patients. Plasma DAO (19 ± 4.8) was increased (P< 0.001) in 27 adult heterozygotes; 10 (37%) had values > +2 S.D. for normal adults. One or more poly amines and/or DAO were increased in each of 11 heterozygotes in whom all parameters were measured. These composite abnormalities might be considered as a potential means for identification of asymptomatic CF heterozygotes. Speculation: Controversy has arisen as to whether an abnormality in polyamine metabolism is present in patients with cystic fibrosis. The present data suggest that altered levels of circulating polyamines do indeed exist and represent a failure of circulating polyamines to decrease with age in individuals homozygous and heterozygous for the cystic fibrosis gene(s). The resulting increase in circulating levels of one or more of the 3 polyamines studied, plus increases in the amine-metabolizing enzyme diamine oxidase, might provide one useful index for identifying adult heterozygotes.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health