Detection of cystic fibrosis homozygotes and heterozygotes with plasma [letter].

Dr Hosli and Esther Vogt base their diagnosis of heterozygotes and homozygotes 
for cystic fibrosis on the thermal stability in plasma or extracellular 
fluids of alpha-mannosidase and/or phosphatase activity assayed at pH 5.4. The 
activity of alpha-mannosidase in plasma and this pH is a composite 
one: both acidic alpha-mannosidase, which has a pH optimum of 4.25 
and intermediate alpha-mannosidase, which has a pH optimum of 5.6 - 
6.0, will contribute to the activity measured at pH 5.4. These 
two forms of alpha-mannosidase are structurally and genetically distinct and have 
different kinetics and thermostabilities. Therefore the total alpha-mannosidase activity at pH 
5.4 and the physicochemical properties of this activity will depend upon 
the relative proportions of the two types of alpha-mannosidase in the 
sample. The proportions of the two forms vary widely in normal 
plasma, especially in plasma from children. Although the data of Hosli 
and Vogt suggest that the total alpha-mannosidase at pH 5.4 does 
not differ significantly between controls, CF heterozygotes and CF homozygotes, they 
do not show whether the proportions of acidic and intermediate alpha-mannosidase 
have changed. An increase in the proportion of the thermolabile intermediate 
alpha-mannosidase in CF would be manifested as a decreased thermostability of 
alpha-mannosidase at pH 5.4. Alternatively a mutation in the normally stable 
acidic alpha-mannosidase leading to a less stable form would also be 
reflected as a decreased stability in the activity at pH 5.4, 
especially if the proportion of acidic alpha-mannosidase was increased in CF. 
These situations should also be considered as possible explanations of the 
observations, in addition to the one favoured by Hosli and Vogt. 
