C Danesino

E Rolle

E Vittonatto

G Comi

L Chiadò-Piat

L Vercelli

M Spada

S Grifoni

T Mongini

BMC Musculoskeletal Disorders

English

Crossref

POSTER PRESENTATION Open AccessHeterozygous individuals with mild phenotype inlate-onset glycogen storage disease type 2:a new cohort of patients?L Vercelli*, E Vittonatto, S Grifoni, L Chiadò-Piat, E Rolle, M Spada, C Danesino, G Comi, T MonginiFrom Proceedings of the 6th European Symposium: Steps Forward in Pompe DiseaseBerlin, Germany. 23-24 November 2012IntroductionLate-onset glycogen storage disease type 2 (GSD2) is agenetic but heterogeneous disorder, which may presentanywhere along a continuum of severity from an iso-lated hyperCKemia to a profound, generalized muscleweakness with pulmonary involvement. The gold stan-dard for diagnosis is confirmation of low or absentlevels of acid alpha-glucosidase (GAA) enzyme activity(usually in the range of 1-40% of normal levels), whichis confirmed only in some cases by molecular analysis ofthe GAA gene. In the literature, heterozygous individualsare usually considered to be asymptomatic, althoughthey can have reduced enzymatic activity. Since enzymereplacement therapy (ERT) became available in 2006, ithas improved the prognosis for severe infantile-onsetPompe disease, as well as for late-onset forms byimproving muscle/respiratory function and/or stabilizingclinical progression. Because the disease is now treata-ble, it is essential to understand which patients maybenefit from ERT.ResultsIn the database of the Centre for Neuromuscular Dis-eases, we found 7 patients with only one mutated GAAallele: 2 female patients showed proximal weakness,pathologic muscular biopsy and reduced GAA enzymeactivity in muscle tissue. These patients started ERTfour years ago, and now there is no evidence of diseaseprogression. The other 5 subjects (two are familiarcases, one father and his son) have mild signs of myopa-thy (i.e., slight scoliosis, proximal weakness, hyperlordo-sis, fatigability, recurrent episodes of respiratory deficit)or isolated hyperCKemia. Muscle biopsies showed non-specific signs, and reduced enzymatic activity (below40%) was confirmed in all patients using at least twomethods (dried blood spot and/or leukocytes and/ormuscle homogenate).ConclusionHeterozygotes with one GAA gene mutation are notalways asymptomatic individuals; in our experience, theycan develop a mild myopathy, have non-specific musclebiopsy results, and reduced GAA enzyme activity. Wefollowed and monitored this cohort of patients (notreceiving ERT) and found that they did develop clinicalevidence of disease. In conclusion, mild symptomaticsubjects and heterozygotes are an emerging group ofpatients. Further molecular investigations and follow-upare required to identify patients in this cohort that maybenefit from ERT.Published: 29 May 2013doi:10.1186/1471-2474-14-S2-P12Cite this article as: Vercelli et al.: Heterozygous individuals with mildphenotype in late-onset glycogen storage disease type 2: a new cohortof patients? BMC Musculoskeletal Disorders 2013 14(Suppl 2):P12.Centre for Neuromuscular Diseases, Department of Neuroscience, Universityof Turin, Turin, ItalyVercelli et al. BMC Musculoskeletal Disorders 2013, 14(Suppl 2):P12http://www.biomedcentral.com/1471-2474/14/S2/P12© 2013 Vercelli et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

Heterozygous individuals with mild phenotype in late-onset glycogen storage disease type 2: a new cohort of patients?

https://bmcmusculoskeletdisord.biomedcentral.com/track/pdf/10.1186/1471-2474-14-S2-P12?site=bmcmusculoskeletdisord.biomedcentral.com

Heterozygous individuals with mild phenotype in late-onset glycogen storage disease type 2: a new cohort of patients?

Abstract

Similar works

Full text

Available Versions

Crossref