Prevalence of Pompe disease in 3,076 patients with hyperCKemia and limb-girdle muscular weakness.

Abstract

OBJECTIVE:

We prospectively screened a large European cohort of patients presenting with hyperCKemia and/or limb-girdle muscular weakness (LGMW) for acid α-glucosidase (GAA) deficiency by dried blood spot (DBS) investigation.

METHODS:

DBS were collected from 3,076 consecutive adult patients from 7 German and British neuromuscular centers. All specimens were investigated for GAA deficiency by fluorometry. Samples with reduced enzyme activity were subsequently investigated for GAA gene mutations.

RESULTS:

Of 3,076 patients with DBS samples, 232 patients (7.6%) showed low GAA enzyme activity. Of these 232 patients, 55 (24%) presented with isolated hyperCKemia and 176 (76%) with hyperCKemia and LGMW. With both features present, 94% of the patients showed a low enzymatic activity. Mutational analysis found GAA gene mutations in 74 patients (2.4%); herein 70 patients were heterozygote for the common GAA gene splice-site mutation c.-32-13T>G. The most common clinical presentation in the confirmed Pompe cohort was a limb-girdle phenotype (85.3%) combined with ventilatory insufficiency (61%). Isolated hyperCKemia was found in 12%, while 2.7 had hyperCKemia and ventilatory insufficiency only.

CONCLUSIONS:

In a large cohort of unselected adult patients with hyperCKemia and/or LGMW, we found a prevalence of late-onset Pompe disease of 2.4%. Therefore, targeted screening of such a population should be encouraged in clinical practice.

• Authors: Zoltan Lukacs, Paulina Nieves Cobos, Stephan Wenninger, Tracey A Willis, Michela Guglieri, Marc Roberts, Rosaline Quinlivan, David Hilton-Jones, Teresinha Evangelista, Stephan Zierz, Beate Schlotter-Weigel, Maggie C Walter, Peter Reilich, Thomas Klopstock, Marcus Deschauer, Volker Straub, Wolfgang Müller-Felber, Benedikt Schoser
• Journal: Neurology (Neurology) Vol. 87 Issue 3 Pg. 295-8 (Jul 19 2016) ISSN: 1526-632X [Electronic] United States
• PMID: 27170567 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2016 American Academy of Neurology.

Chemical References

• Creatine Kinase
• alpha-Glucosidases

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Creatine Kinase (blood)
• Dried Blood Spot Testing
• Female
• Germany (epidemiology)
• Glycogen Storage Disease Type II (blood, complications, epidemiology, genetics)
• Humans
• Male
• Middle Aged
• Muscular Dystrophies, Limb-Girdle (complications, enzymology, epidemiology, genetics)
• Mutation
• Phenotype
• Prevalence
• United Kingdom (epidemiology)
• Young Adult
• alpha-Glucosidases (blood, deficiency, genetics)