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

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.

[1]  Z. Lukacs,et al.  Targeted screening for the detection of Pompe disease in patients with unclassified limb-girdle muscular dystrophy or asymptomatic hyperCKemia using dried blood: A Spanish cohort , 2015, Neuromuscular Disorders.

[2]  S. García-Morillo,et al.  Delayed diagnosis of late-onset Pompe disease in patients with myopathies of unknown origin and/or hyperCKemia. , 2015, Molecular genetics and metabolism.

[3]  G. Comi,et al.  LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population , 2015, Journal of Neurology, Neurosurgery & Psychiatry.

[4]  S. Kiuru-Enari,et al.  Screening for late-onset Pompe disease in Finland , 2014, Neuromuscular Disorders.

[5]  J. Vissing,et al.  Late-onset Pompe disease is prevalent in unclassified limb-girdle muscular dystrophies. , 2013, Molecular genetics and metabolism.

[6]  P. Kishnani,et al.  Timing of diagnosis of patients with pompe disease: Data from the pompe registry , 2013, American journal of medical genetics. Part A.

[7]  G. Comi,et al.  Screening for later-onset Pompe's disease in patients with paucisymptomatic hyperCKemia. , 2013, Molecular genetics and metabolism.

[8]  B. Schoser,et al.  Enzyme replacement therapy in late-onset Pompe disease: a systematic literature review , 2013, Journal of Neurology.

[9]  B. Schoser,et al.  Toward deconstructing the phenotype of late‐onset Pompe disease , 2012, American journal of medical genetics. Part C, Seminars in medical genetics.

[10]  W. Hop,et al.  Survival and associated factors in 268 adults with Pompe disease prior to treatment with enzyme replacement therapy , 2011, Orphanet journal of rare diseases.

[11]  Z. Lukacs,et al.  Diagnostic efficacy of the fluorometric determination of enzyme activity for Pompe disease from dried blood specimens compared with lymphocytes—possibility for newborn screening , 2010, Journal of Inherited Metabolic Disease.

[12]  D. Millington,et al.  Screening for pompe disease using a rapid dried blood spot method: Experience of a clinical diagnostic laboratory , 2009, Muscle & nerve.

[13]  A. Reuser,et al.  Pompe's disease , 2008, The Lancet.

[14]  J. Melvin.  Pompe's disease. , 2000, Archives of neurology.