Prevalence of Pompe disease in 3,076 patients with hyperCKemia and limb-girdle muscular weakness
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Prevalence of Pompe disease in 3,076 patients with hyperCKemia and limb-girdle muscular weakness. / Lukacs, Zoltan; Nieves Cobos, Paulina; Wenninger, Stephan; Willis, Tracey A; Guglieri, Michela; Roberts, Marc; Quinlivan, Rosaline; Hilton-Jones, David; Evangelista, Teresinha; Zierz, Stephan; Schlotter-Weigel, Beate; Walter, Maggie C; Reilich, Peter; Klopstock, Thomas; Deschauer, Marcus; Straub, Volker; Müller-Felber, Wolfgang; Schoser, Benedikt.
In: NEUROLOGY, Vol. 87, No. 3, 19.07.2016, p. 295-8.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Prevalence of Pompe disease in 3,076 patients with hyperCKemia and limb-girdle muscular weakness
AU - Lukacs, Zoltan
AU - Nieves Cobos, Paulina
AU - Wenninger, Stephan
AU - Willis, Tracey A
AU - Guglieri, Michela
AU - Roberts, Marc
AU - Quinlivan, Rosaline
AU - Hilton-Jones, David
AU - Evangelista, Teresinha
AU - Zierz, Stephan
AU - Schlotter-Weigel, Beate
AU - Walter, Maggie C
AU - Reilich, Peter
AU - Klopstock, Thomas
AU - Deschauer, Marcus
AU - Straub, Volker
AU - Müller-Felber, Wolfgang
AU - Schoser, Benedikt
N1 - © 2016 American Academy of Neurology.
PY - 2016/7/19
Y1 - 2016/7/19
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Creatine Kinase
KW - Dried Blood Spot Testing
KW - Female
KW - Germany
KW - Glycogen Storage Disease Type II
KW - Humans
KW - Male
KW - Middle Aged
KW - Muscular Dystrophies, Limb-Girdle
KW - Mutation
KW - Phenotype
KW - Prevalence
KW - United Kingdom
KW - Young Adult
KW - alpha-Glucosidases
KW - Journal Article
KW - Multicenter Study
U2 - 10.1212/WNL.0000000000002758
DO - 10.1212/WNL.0000000000002758
M3 - SCORING: Journal article
C2 - 27170567
VL - 87
SP - 295
EP - 298
JO - NEUROLOGY
JF - NEUROLOGY
SN - 0028-3878
IS - 3
ER -