ANALYSIS OF CREATINE-KINASE ACTIVITY IN 504 PATIENTS WITH PROXIMAL SPINAL MUSCULAR-ATROPHY TYPES I-III FROM THE POINT-OF-VIEW OF PROGRESSION AND SEVERITY

Mild to moderately elevated creatine kinase (CK) activity is a frequen t biochemical finding in proximal spinal muscular atrophy (SMA). In a collaborative study on all types of childhood and juvenile onset SMA, we analysed the CK activity of 504 SMA patients (138 type I, 127 type II, 144 type IIIa, and 95 type IIIb patients). Under the assumption of a lognormal distribution of CK activity as the most appropriate stati stical model, CK levels were transformed into logarithms and compared by standard deviation scores = CK-SDS (log). CK activity was statistic ally different between early and later onset SMA: in SMA I and II, abo ut one-third of patients showed CK-SDS (log) >2 SD, the analysis of th e means did not show significant differences. In SMA III, CK-SDS (log) was significantly higher (p < 0.01) than in the two other groups, whi ch was most pronounced in SMA IIIb. More than 90% of SMA IIIb patients showed CK-SDS (log) values >2 vs. 57% in SMA IIIa. As similar values were obtained for a subgroup of 100 patients in whom the diagnosis of autosomal recessive SMA was confirmed by a deletion of the telomeric c opy of the survival motor neuron gene, our results can be considered r epresentative for SMA I-III. There was no correlation between CK level and disease duration. The fact that patients were ambulatory or chair -bound had no influence on CK activity in type III SMA. There was no s ex influence in SMA I, II and IIIa. The observed higher male values in the group SMA IIIb are most likely the result of a lack of female pat ients with onset after puberty.