CATHEPSIN-A DEFICIENCY IN GALACTOSIALIDOSIS - STUDIES OF PATIENTS ANDCARRIERS IN 16 FAMILIES

Deficiency of lysosomal protective protein/cathepsin A in humans is th e primary cause of galactosialidosis, a lysosomal storage disease char acterized by combined deficiency of beta-galactosidase and neuraminida se. We have investigated 20 galactosialidosis patients and nine of the ir obligate heterozygous parents, A group of 12 patients with the earl y infantile type of the disease exhibited practically complete absence of cathepsin A activity, whereas eight patients with either the late infantile or the juvenile/adult type had 2-5% residual activity. Highe st levels (5%) were present in two patients with milder clinical manif estations and later onset of the disease. In most fibroblast strains, beta-galactosidase activity was 10-15% of normal levels, whereas neura minidase was reduced to less than 4%. Interestingly, a substantial res idual activity (10%) of the latter enzyme was detected in the patient with the mildest phenotype and the highest cathepsin A activity. Heter ozygous values for cathepsin A were reduced on average to half of norm al levels. However, in two cell strains, the activity was far below co ntrol range, and in these cases, neuraminidase activity was severely d epressed. Finally, we showed that cathepsin A had considerable activit y in chorionic villi and amniocytes, but was deficient in amniocytes f rom a pregnancy with an affected fetus, indicating the relevance of ca thepsin A assay for prenatal diagnosis of galactosialidosis.