Diagnosis of Pompe disease in different age groups using a dried blood spot assay. D. Bali, M. Changela, JL. Goldstein, SP. Young, PS. Kishnani, H. Zhang, J. Dai, DS. Millington Dept Pediatric Med Genetics, Duke Univ Medical Ctr, Durham, NC.
Pompe Disease (acid maltase deficiency; Glycogen Storage disease type II) is caused by a deficiency of the lysosomal enzyme, acid alpha-glucosidase (GAA). GAA deficiency results in glycogen accumulation in multiple tissues, particularly skeletal, cardiac and smooth muscles. Measurement of GAA activity in dried blood spots (DBS) (Zhang et al, Genet. Med. 2006, 8: 302-306) is a rapid and reliable method for diagnosing Pompe disease, being less invasive than assays in cultured skin fibroblasts or muscle biopsies. We report our diagnostic experience of this assay, in both younger (3 yrs) and older ( 3 yrs) patient populations, including correlation with urinary tetrasaccharide biomarker, GAA activity in fibroblasts and muscle and DNA mutation analysis. In the older patient population we have reviewed the reported clinical indications for testing, including symptoms of limb girdle muscular dystrophy and other myopathies that resemble late-onset Pompe disease. 18% of younger patients tested (14 of 79) had DBS GAA deficiency, and follow-up testing was performed in 9 patients for whom samples were received. 12 of 14 younger patients were referred because of cardiomyopathy. A similar incidence of GAA deficiency (20%; 45 of 220 samples) was observed for older patients and follow-up testing was performed for 19. Muscle weakness (71%) was the most common reason for testing in the older patient population. One third of these cases were defined as proximal muscle weakness and 2/3rd were undefined. Family history (21%) was the second most common reason. 16% of the older patient group were reported to have respiratory involvement. The majority of patients (>50%) were referred from genetics or neurology clinics. Approximately 20% of tested patient population had GAA activity below the control range, but above the range for known affected patients. Additional testing was recommended for these patients. These results will aid our understanding of patients who will benefit from DBS GAA testing. Correlation with other diagnostic tests will improve recommendations for confirmatory testing.