Abstract
Pompe disease is an autosomal recessive disorder of glycogen metabolism caused by a deficiency of the lysosomal enzyme acid α-glucosidase (GAA). It presents at any age, with variable rates of progression ranging from a rapidly progressive course, often fatal by one-year of age, to a more slowly, but nevertheless relentlessly progressive course, resulting in significant morbidity and premature mortality. In infants, early initiation of enzyme replacement therapy is needed to gain the maximum therapeutic benefit, underscoring the need for early diagnosis. Several new methods for measuring GAA activity have been developed. The Pompe Disease Diagnostic Working Group met to review data generated using the new methods, and to establish a consensus regarding the application of the methods for the laboratory diagnosis of Pompe disease. Skin fibroblasts and muscle biopsy have traditionally been the samples of choice for measuring GAA activity. However, new methods using blood samples are rapidly becoming adopted because of their speed and convenience. Measuring GAA activity in blood samples should be performed under acidic conditions (pH 3.8-4.0), using up to 2 mM of the synthetic substrate 4-methylumbelliferyl-α-d-glucoside or glycogen (50 mg/mL), in the presence of acarbose (3-9 μM) to inhibit the isoenzyme maltase-glucoamylase. The activity of a reference enzyme should also be measured to confirm the quality of the sample. A second test should be done to support the diagnosis of Pompe disease until a program for external quality assurance and proficiency testing of the enzymatic diagnosis in blood is established.
| Original language | English |
|---|---|
| Pages (from-to) | 275-281 |
| Number of pages | 7 |
| Journal | Molecular Genetics and Metabolism |
| Volume | 93 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2008 |
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Keywords
- Acarbose
- Acid maltase deficiency
- Diagnosis
- Enzyme assay
- Glycogen storage disease type II
- Lysosomal acid α-glucosidase
- Pompe disease
ASJC Scopus subject areas
- Biochemistry
- Genetics
- Endocrinology, Diabetes and Metabolism
Cite this
Methods for a prompt and reliable laboratory diagnosis of Pompe disease : Report from an international consensus meeting. / Winchester, B.; Bali, D.; Bodamer, O. A.; Caillaud, C.; Christensen, E.; Cooper, A.; Cupler, E.; Deschauer, M.; Fumić, K.; Jackson, M.; Kishnani, P.; Lacerda, L.; Ledvinová, J.; Lugowska, A.; Lukacs, Z.; Maire, I.; Mandel, H.; Mengel, E.; Müller-Felber, W.; Piraud, M.; Reuser, A.; Rupar, T.; Sinigerska, I.; Szlago, M.; Verheijen, F.; van Diggelen, O. P.; Wuyts, B.; Zakharova, E.; Keutzer, J.
In: Molecular Genetics and Metabolism, Vol. 93, No. 3, 01.03.2008, p. 275-281.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Methods for a prompt and reliable laboratory diagnosis of Pompe disease
T2 - Report from an international consensus meeting
AU - Winchester, B.
AU - Bali, D.
AU - Bodamer, O. A.
AU - Caillaud, C.
AU - Christensen, E.
AU - Cooper, A.
AU - Cupler, E.
AU - Deschauer, M.
AU - Fumić, K.
AU - Jackson, M.
AU - Kishnani, P.
AU - Lacerda, L.
AU - Ledvinová, J.
AU - Lugowska, A.
AU - Lukacs, Z.
AU - Maire, I.
AU - Mandel, H.
AU - Mengel, E.
AU - Müller-Felber, W.
AU - Piraud, M.
AU - Reuser, A.
AU - Rupar, T.
AU - Sinigerska, I.
AU - Szlago, M.
AU - Verheijen, F.
AU - van Diggelen, O. P.
AU - Wuyts, B.
AU - Zakharova, E.
AU - Keutzer, J.
PY - 2008/3/1
Y1 - 2008/3/1
N2 - Pompe disease is an autosomal recessive disorder of glycogen metabolism caused by a deficiency of the lysosomal enzyme acid α-glucosidase (GAA). It presents at any age, with variable rates of progression ranging from a rapidly progressive course, often fatal by one-year of age, to a more slowly, but nevertheless relentlessly progressive course, resulting in significant morbidity and premature mortality. In infants, early initiation of enzyme replacement therapy is needed to gain the maximum therapeutic benefit, underscoring the need for early diagnosis. Several new methods for measuring GAA activity have been developed. The Pompe Disease Diagnostic Working Group met to review data generated using the new methods, and to establish a consensus regarding the application of the methods for the laboratory diagnosis of Pompe disease. Skin fibroblasts and muscle biopsy have traditionally been the samples of choice for measuring GAA activity. However, new methods using blood samples are rapidly becoming adopted because of their speed and convenience. Measuring GAA activity in blood samples should be performed under acidic conditions (pH 3.8-4.0), using up to 2 mM of the synthetic substrate 4-methylumbelliferyl-α-d-glucoside or glycogen (50 mg/mL), in the presence of acarbose (3-9 μM) to inhibit the isoenzyme maltase-glucoamylase. The activity of a reference enzyme should also be measured to confirm the quality of the sample. A second test should be done to support the diagnosis of Pompe disease until a program for external quality assurance and proficiency testing of the enzymatic diagnosis in blood is established.
AB - Pompe disease is an autosomal recessive disorder of glycogen metabolism caused by a deficiency of the lysosomal enzyme acid α-glucosidase (GAA). It presents at any age, with variable rates of progression ranging from a rapidly progressive course, often fatal by one-year of age, to a more slowly, but nevertheless relentlessly progressive course, resulting in significant morbidity and premature mortality. In infants, early initiation of enzyme replacement therapy is needed to gain the maximum therapeutic benefit, underscoring the need for early diagnosis. Several new methods for measuring GAA activity have been developed. The Pompe Disease Diagnostic Working Group met to review data generated using the new methods, and to establish a consensus regarding the application of the methods for the laboratory diagnosis of Pompe disease. Skin fibroblasts and muscle biopsy have traditionally been the samples of choice for measuring GAA activity. However, new methods using blood samples are rapidly becoming adopted because of their speed and convenience. Measuring GAA activity in blood samples should be performed under acidic conditions (pH 3.8-4.0), using up to 2 mM of the synthetic substrate 4-methylumbelliferyl-α-d-glucoside or glycogen (50 mg/mL), in the presence of acarbose (3-9 μM) to inhibit the isoenzyme maltase-glucoamylase. The activity of a reference enzyme should also be measured to confirm the quality of the sample. A second test should be done to support the diagnosis of Pompe disease until a program for external quality assurance and proficiency testing of the enzymatic diagnosis in blood is established.
KW - Acarbose
KW - Acid maltase deficiency
KW - Diagnosis
KW - Enzyme assay
KW - Glycogen storage disease type II
KW - Lysosomal acid α-glucosidase
KW - Pompe disease
UR - http://www.scopus.com/inward/record.url?scp=38949192583&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38949192583&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2007.09.006
DO - 10.1016/j.ymgme.2007.09.006
M3 - Article
C2 - 18078773
AN - SCOPUS:38949192583
VL - 93
SP - 275
EP - 281
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
SN - 1096-7192
IS - 3
ER -