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Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating
Author(s) -
Kroos Marian,
Pomponio Robert J.,
van Vliet Laura,
Palmer Rachel E.,
Phipps Michael,
Van der Helm Robert,
Halley Dicky,
Reuser Arnold
Publication year - 2008
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20745
Subject(s) - glycogen storage disease type ii , biology , failure to thrive , glycogen storage disease , disease , exercise intolerance , weakness , mutation , missense mutation , genetics , bioinformatics , heart failure , gene , medicine , enzyme replacement therapy , glycogen , endocrinology , anatomy
Pompe disease was named after the Dutch pathologist Dr JC Pompe who reported about a deceased infant with idiopathic hypertrophy of the heart. The clinical findings were failure to thrive, generalized muscle weakness and cardio‐respiratory failure. The key pathologic finding was massive storage of glycogen in heart, skeletal muscle and many other tissues. The disease was classified as glycogen storage disease type II and decades later shown to be a lysosomal disorder caused by acid α‐glucosidase deficiency. The clinical spectrum of Pompe disease appeared much broader than originally recognized. Adults with the same enzyme deficiency, alternatively named acid maltase deficiency, were reported to have slowly progressive skeletal muscle weakness and respiratory problems, but no cardiac involvement. The clinical heterogeneity is largely explained by the kind and severity of mutations in the acid α‐glucosidase gene ( GAA ), but secondary factors, as yet unknown, have a substantial impact. The Pompe disease mutation database aims to list all GAA sequence variations and describe their effect. This update with 107 sequence variations (95 being novel) brings the number of published variations to 289, the number of non‐pathogenic mutations to 67 and the number of proven pathogenic mutations to 197. Further, this article introduces a tool to rate the various mutations by severity, which will improve understanding of the genotype‐phenotype correlation and facilitate the diagnosis and prognosis in Pompe disease. © 2008 Wiley‐Liss, Inc.