Fróðskaparrit - 01.01.1975, Page 11

Amylo-l,6-glucosidase deficiency
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it is obvious that a diagnosis of heterozygosity cannot be estab-
ished in singie individuals by this method. Healthy sibs of
patients (with a chance of being heterozygous of 67 °/o) and
sibs of parents of patients (with a chance of heterozygosity
around 50 °/o) have as expected medial values between those
seen in definite heterozygotes and in normals.
The determination of enzyme activity in the erythrocytes
does not permit any distinction between patients and definite
heterozygotes. It is possible that the presence of measurable
activity in the patients is an artifact due to unspecific binding
of radioactive glucose to glycogen and protein in the assay;
this may also take place in the assay of the enzyme in leuco-
cytes, but the results here show zero activity in the patients,
corresponding to the much lower protein concentration ín this
assay. The median value of erythrocyte activity in normals is
much higher than that of the patients and the heterozygotes,
but the distributions overlap considerably. Thus, the examina-
tion of erythrocytes by the methods adopted here is less in-
formative than the study of leucocyte activity.
It seems clear that more reliable methods of defining hetero-
zygotes are needed for practical as well as theoretical purposes.
Genetic counselling cannot be sufficiently exact as long as such
methods are lacking, and they will be needed if more effective
preventive measures such as screening of newborns in this and
other high risk populations are to be introduced. Linkage ana-
lyses would also have to await the appearance of methods for
reliable heterozygote detection. The present suggestion of a
possible association between the gene determining ADA vari-
ants and enzyme activity may be due to chance alone as a
considerable number of tests for association was performed.
It might, however, be worthwile to attempt studies of the
genetic relation between the genetic ADA variation and amylo-
1,6-glucosidase deficiency by somatic cell hybridization; posi-
tive results obtained in this way could be of high value in
the continued studies which aim at a more complete elucidation
of type III glycogenosis.