Pompe Disease

Prenatal 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.

A recent study has explored the use of plasma and dried blood spots to test for Pompe disease in newborns.^[3] It remains to be seen how reliable or accepted this diagnostic technique will be in common practice, however.

References

1. Hirschhorn, Rochelle and Arnold J. J. Reuser. Glycogen Storage Disease Type II: Acid-Alpha Glucosidase (Acid Maltase) Deficiency. In: Wonsiewicz M, Noujaim S, Boyle P, eds. 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: Wonsiewicz M, Noujaim S, Boyle P, eds. 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.