Symptomatic Heterozygosity due to Definite GAA Mutations in Late-Onset Pompe Disease

Abstract

members of the third generation of a late-onset Pompe disease family which counts 36 individuals. Clinical, laboratory, and GAA enzymatic and genetic studies disclosed widespread myalgias and low back pain as well as mild weakness of the pelvic girdle muscles in 5 individuals (3 females, 2 males; aged 24–30 years), 3 of whom had a slight increase in CPK. Symptom onset was during the second decade of life. GAA enzyme activity ranged from 2 to 4 μmol/h/L in all patients. Direct sequencing of the GAA gene carrying the mutations, previously identifi ed in their parents, disclosed the R40X mutation in the 5 symptomatic individuals, whereas the splicing Symptomatic Heterozygosity due to Defi nite GAA Mutations in Late-Onset Pompe Disease