An integrative correlation of myopathology, phenotype and genotype in late onset Pompe disease.

AIMS: Pompe disease is caused by pathogenic mutations in the alpha 1,4-glucosidase (GAA) gene and in patients with late onset Pome disease (LOPD), genotype-phenotype correlations are unpredictable. Skeletal muscle pathology includes glycogen accumulation and altered autophagy of various degrees. A correlation of the muscle morphology with clinical features and the genetic background in GAA may contribute to the understanding of the phenotypic variability. METHODS: Muscle biopsies taken before enzyme replacement therapy were analysed from 53 patients with LOPD. On resin sections, glycogen accumulation, fibrosis, autophagic vacuoles and the degree of muscle damage (morphology-score) were analysed and the results were compared with clinical findings. Additional autophagy markers microtubule-associated protein 1A/1B-light chain 3, p62 and Bcl2-associated athanogene 3 were analysed on cryosections from 22 LOPD biopsies. RESULTS: The myopathology showed a high variability with, in most patients, a moderate glycogen accumulation and a low morphology-score. High morphology-scores were associated with increased fibrosis and autophagy highlighting the role of autophagy in severe stages of skeletal muscle damage. The morphology-score did not correlate with the patient's age at biopsy, disease duration, nor with the residual GAA enzyme activity or creatine-kinase levels. In 37 patients with LOPD, genetic analysis identified the most frequent mutation, c.-32-13T>G, in 95%, most commonly in combination with c.525delT (19%). No significant correlation was found between the different GAA genotypes and muscle morphology type. CONCLUSIONS: Muscle morphology in LOPD patients shows a high variability with, in most cases, moderate pathology. Increased pathology is associated with more fibrosis and autophagy.

Searching for balanced development.

PIP: It is significant in China, as the day of 5 billion is commemorated, that the Government has shown its full committment to a family planning program that has been internationally acknowledged as one of the most successful efforts in the world today. Since 1979, the annual population growth rate in China has gone down from 2.7% to an annual average of around 1.2%. In fact, because China makes up more than 1/5 of the world's population, the overall growth rate achieved worldwide has been reduced to about 2%. This is heavily due to the achievements of the Chinese family planning program. Even as China has lowered its birthrate, its rate of agricultural production has rapidly risen. At present, China is doing well in grain production. Although the per capita income in China is still comparatively low, the country is able to feed its citizens, and the famines that used to be a big problem are now but a bad memory. As the close relationship between population and development is observed, there is some controversy about the effects and impact of family planning on development. The belief is held that the more people there are in this world, the more progress there will be because more brains, hands, and energy will be harnessed for development. As has also been noted, however, a person is not just head and hands--a person has a mouth to feed, as well. Thus, there is a need to balance the number of people with the resources of the society. If the rate of population growth outstrips economic and social production, then hunger and poverty will result, as the fruits of development will be eaten up too rapidly.^ieng