Overview of Pompe Disease
Diagnosing Pompe
Clinical Manifestations
Prenatal ScreeningPrenatal Screening
Prenatal diagnosis is available for Pompe disease in cases where it may be warranted, such as subsequent pregnancies in families with an affected child or when a parent presents with the late-onset form.
In fact, Pompe disease was one of the first genetic disorders for which researchers attempted diagnosis prior to birth using amniocentesis, with the first published reports appearing in the late 1960s.1
Today, prenatal diagnosis can be made with either amniocentesis or, more commonly, direct enzyme analysis of uncultured chorionic villi cells, primarily using 4-methylumbelliferyl-a-D-glucoside (4MUG) as substrate. 4MUG is a substance upon which the acid alpha-glucosidase (GAA) enzyme acts.
The direct enzyme analysis of uncultured chorionic villi cells offers additional benefits as it allows for early diagnosis (12th week of pregnancy) and potentially as quick as a one day turnaround for results.2 In some cases, DNA analysis may also be used as a supportive method to confirm a prenatal diagnosis of Pompe disease when the particular defect involved is known. In addition, it can enable definitive carrier detection in the patient's family.
Testing in Newborns
Currently, Pompe disease is diagnosed by the virtual absence, in infantile-onset, or reduction, in late-onset, of acid alpha-glucosidase activity in muscle biopsies, cultured fibroblasts, and lymphocyte blood tests. Two of these assays are invasive and not suited to large-scale screening.3
A recent study has explored the use of plasma and dried blood spots to test for Pompe disease in newborns. Dried blood spots could provide a simple, noninvasive source for screening for GAA activity. These tests are validated but not yet commercially available.3 This test can easily be incorporated into newborn screening due to performance, speed, and cost factors. And it also demonstrated a sensitivity and specificity of 100% for identification of affected individuals.4
References
1. Hirschhorn, Rochelle and Arnold J. J. Reuser. Glycogen Storage Disease Type II: Acid-Alpha Glucosidase (Acid Maltase) Deficiency. In: Scriver C, Beaudet A, Sly W, Valle D, editors. The Metabolic and Molecular Bases of Inherited Disease. 8th Edition. New York: McGraw-Hill; 2001; 3389-3420.
2. Hirschhorn, Rochelle and Arnold J. J. Reuser. Glycogen Storage Disease Type II: Acid-Alpha Glucosidase (Acid Maltase) Deficiency. In: Scriver C, Beaudet A, Sly W, Valle D, editors. The Metabolic and Molecular Bases of Inherited Disease. 8th Edition. New York: McGraw-Hill; 2001; 3389-3420.
3. Umapathysivam K, Whittle AM, Ranieri E, et al. Determination of acid alpha-glucosidase protein:
evaluation as a screening marketer for Pompe disease and other lysosomal storage disorders. Clin Chem
2000 Sep; 46(9): 1318-25.
4. Chamoles NA, Niizawa G, Blanco M, Gaggiolo D, Casentiini C. Glycogen storage disease type II: enzymatic screening in dried blood spots on filter paper. Clin Chimica Acta. [in press]
