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Orphanet Journal of Rare Diseases

, 7:88

First Online: 12 November 2012Received: 01 October 2012Accepted: 06 November 2012


BackgroundDue partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression.

MethodsWe conducted a single-center, prospective, observational study. Muscle strength manual muscle testing, and hand-held dynamometry, muscle function quick motor function test, and pulmonary function forced vital capacity in sitting and supine positions were assessed every 3–6 months and analyzed using repeated-measures ANOVA.

ResultsBetween October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis 23%, bulbar weakness 28%, and scapular winging 33%. During follow-up average 1.6 years, range 0.5-4.2 years, skeletal muscle strength deteriorated significantly mean declines of −1.3% point-year for manual muscle testing and of −2.6% points-year for hand-held dynamometry; both p<0.001. Longer disease duration >15 years and pulmonary involvement forced vital capacity in sitting position <80% at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year p=0.02. Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast.

ConclusionsRecognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when.

KeywordsAcid α-glucosidase Glycogen storage disease type II OMIM number 232300 Lysosomal storage disorder Disease progression Natural course Prognostic factors Abbreviations4-MU4-methylumbelliferyl-α-D-glucopyranoside

ATSAmerican Thoracic Society

CCMOCentral Committee on Research Involving Human Subjects in the Netherlands

CKCreatine Kinase

ERSEuropean Respiratory Society

ERTEnzyme Replacement Therapy

FSHDFacioScapuloHumeral Dystrophy

FVCForced Vital Capacity

GAAGene coding for acid alpha-glucosidase

HHDHand-held dynamometry

LGMDLimb-Girdle Muscular Dystrophy

MRCMedical Research Council

Pp-yPercentage points per year

QMFTQuick Motor Function Test

QMTQuantitative Muscle Testing.

Electronic supplementary materialThe online version of this article doi:10.1186-1750-1172-7-88 contains supplementary material, which is available to authorized users.

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Autor: Nadine AME van der Beek - Juna M de Vries - Marloes LC Hagemans - Wim CJ Hop - Marian A Kroos - John HJ Wokke - Marian


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