Abstract:
:We have established a new method for the enzymatic diagnosis of glycogen storage disease type II (Pompe disease or acid maltase deficiency) using mixed leukocytes. The method employs glycogen and 4-methylumbelliferyl-alpha-D-glucopyranoside (4MU-alphaGlc) as substrates for measuring the lysosomal acid alpha-glucosidase (acid alphaGlu) activity, and incorporates acarbose to eliminate the interference of unrelated alpha-glucosidases (predominantly maltase-glucoamylase). It is shown that 3.0 micromol/L acarbose completely inhibits the maltase-glucoamylase activity at pH 4.0, but the lysosomal acid alphaGlu activity by less than 5%. With this method, we determined the acid alphaGlu activity in mixed leukocytes from 25 patients with glycogen storage disease type II (2 infantile and 23 late-onset cases), one GAA2/GAA2 homozygote and 30 healthy subjects. In the assay with glycogen as substrate, the addition of acarbose created a clear separation between the patient and the control ranges. In the assay with 4MU-alphaGlc as substrate, the two ranges were fully separated but remained very close despite the use of acarbose. The separation of the patient and normal ranges was improved considerably by taking the ratio of acarbose-inhibited over uninhibited activity. A GAA2/GAA2 homozygote was correctly diagnosed with 4MU-alphaGlc but misdiagnosed as patient when glycogen was used as substrate. We conclude that the inclusion of 3.0 micromol/L acarbose in the assays with glycogen and 4MU-alphaGlc substrates at pH 4.0 allows for the specific measurement of lysosomal acid alphaGlu activity in mixed leukocytes, thus enabling a reliable diagnosis of glycogen storage disease type II in this specimen.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Okumiya T,Keulemans JL,Kroos MA,Van der Beek NM,Boer MA,Takeuchi H,Van Diggelen OP,Reuser AJdoi
10.1016/j.ymgme.2005.10.016subject
Has Abstractpub_date
2006-05-01 00:00:00pages
22-8issue
1eissn
1096-7192issn
1096-7206pii
S1096-7192(05)00378-1journal_volume
88pub_type
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