AMP deaminase deficiency in skeletal muscle is unlikely to be of clinical relevance

Background The homozygous c.34C > T mutation in the AMPD1 gene encoding the muscle-specific isoform of AMP deaminase (AMPD) accounts for the vast majority of inherited skeletal muscle AMPD deficiencies. It is controversial (i) whether AMPD deficiency is associated with exercise-induced complaints and (ii) whether an acquired form exists in which an underlying neuromuscular disorder additionally lowers the AMPD activity. Design c.34C > T mutation (homozygous- TT, heterozygous-CT,wildtype-CC) was screened in 107 healthy blood donors and 294 patients with skeletal muscle biopsy including 200 with exercise-induced complaints. Additional screening for c.468G > T and c.860A > T mutations was performed in all CT.AMPD was analysed histochemically and biochemically. Results The mutant allele frequency (MAF) was not different in blood donors, patients with muscle biopsy, and the subgroup with exercise-induced complaints (12.9-16.8 %). CT was found in 63 and TT in 13 patients. The c.468G > T mutation was not detected. The c.860A > T mutation was found in 2.8 % blood donors and 1.6% CT. AMPD activities showed a substantial overlap in CC and CT, but not with TT. AMPD activities in TT, CT, and CC did not differ in patients with a defined neuromuscular disorder and those with only exercise-induced complaints. In TT, CT, and CC there were no differences in the frequency of signs and symptoms, hyperCKemia, or myopathological biopsy pattern. Conclusion MAF did not differ in normal and diseased populations. The frequency of exertion-induced complaints was not higher in TT than CC. There was no specific phenotype of TT and no evidence for an acquired form of AMPD deficiency.