Late-onset glycogen storage disease type 2 (GSD2)/Pompe disease is a progressive multi-system disease evoked by a deficiency of lysosomal acid alpha-glucosidase (GAA) activity. GSD2 is characterized by respiratory and skeletal muscle weakness and atrophy, resulting in functional disability and reduced life span. Since 2006 alglucosidase alfa has been licensed as a treatment in all types of GSD2/Pompe disease. We here present an open-label, investigator-initiated observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 44 late-onset GSD2 patients with various stages of disease severity. Alglucosidase alfa was given i.v. at the standard dose of 20 mg/kg every other week. Assessments included serial arm function tests (AFT), Walton Gardner Medwin scale (WGMS), timed 10-m walk tests, four-stair climb tests, modified Gowers' maneuvers, 6-min walk tests, MRC sum score, forced vital capacities (FVC), creatine kinase (CK) levels and SF-36 self-reporting questionnaires. All tests were performed at baseline and every 3 months for 12 months of ERT. We found significant changes from baseline in the modified Gowers' test, the CK levels and the 6-min walk test (341 +/- 149.49 m, median 342.25 m at baseline; 393 +/- 156.98 m; median 411.50 m at endpoint; p = 0.026), while all other tests were unchanged. ERT over 12 months revealed minor allergic reactions in 10% of the patients. No serious adverse events occurred. None of the patients died or required de novo ventilation. Our clinical outcome data imply stabilization of neuromuscular deficits over 1 year with mild functional improvement.

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Our data denote a rather variable course of neuromuscular deficits in chronic adult-onset Pompe patients during 36 months of alglucosidase alfa ERT.

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The occurrence of hand tremors in patients with spasmodic torticollis (ST) was investigated in 55 patients by clinical and quantitative measurements. Ten patients had first-order or second-order relatives affected with postural tremor. Although 40% of the patients had a medical history and clinical findings for mild postural and action tremor of the hands, only four had moderate tremor amplitudes. One patient had a severe tremor, including resting tremor, and two had mild voice tremor. A positive correlation was found between hand and head tremor. Patients with hand tremor were younger at the onset of ST than were those without. The mean amplitudes of postural tremor were only slightly higher than for the controls and much smaller than those found in classic essential tremor. The tremor caused only mild disabilities. The tremor frequencies were indistinguishable from physiologic tremor. Further analysis of the tremor records showed evidence for physiologic tremor mechanisms only. We conclude that slightly enhanced postural hand tremors are common in ST but have a low amplitude and are only rarely clinically relevant for ST patients. Although the present data support the notion of an enhanced risk of postural tremor in families of patients affected with ST, none of the criteria allowed the separation of the hand tremor of ST from other postural/action tremors and especially from enhanced physiologic tremor. Thus, the present data do not support the classification of hand tremor in ST as either "dystonic" or essential tremor.