Abstract
Glycogen storage disease type II (GSDII) is a lysosomal storage disorder caused by acid alpha-1,4-glucosidase deficiency and associated with recessive mutations in its coding gene GAA. Few studies have provided so far a detailed phenotypical characterization in late onset GSDII (LO-GSDII) patients. Genotype-phenotype correlation has been previously attempted with controversial results. We aim to provide an in-depth description of a cohort (n = 36) of LO-GSDII patients coming from the north of Italy and compare our population's findings to the literature. We performed a clinical record-based retrospective and prospective study of our patients. LO-GSDII in our cohort covers a large variability of phenotype including subtle clinical presentation and did not differ significantly from previous data. In all patients, molecular analysis disclosed GAA mutations, five of them being novel. To assess potential genotype-phenotype correlations we divided IVS1-32-13T>G heterozygous patients into two groups following the severity of the mutations on the second allele. Our patients harbouring "severe" mutations (n = 21) presented a strong tendency to have more severe phenotypes and more disability, more severe phenotypes and more disability, higher prevalence of assisted ventilation and a shorter time of evolution to show it. The determination of prognostic factors is mandatory in order to refine the accuracy of prognostic information, to develop follow-up strategy and, more importantly, to improve the decision algorithm for enzyme replacement therapy administration. The demonstration of genotype-phenotype correlations could help to reach this objective. Clinical assessment homogeneity is required to overcome limitations due to the lack of power of most studies.
| Original language | English |
|---|---|
| Pages (from-to) | 83-97 |
| Number of pages | 15 |
| Journal | Journal of Neurology |
| Volume | 261 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2014 |
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Keywords
- Correlation
- Genotype
- Glycogen storage disease type II (GSDII)
- Phenotype
- Prognosis
- Review
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
Cite this
Extended phenotype description and new molecular findings in late onset glycogen storage disease type II : A northern Italy population study and review of the literature. / Remiche, Gauthier; Ronchi, Dario; Magri, Francesca; Lamperti, Costanza; Bordoni, Andreina; Moggio, Maurizio; Bresolin, Nereo; Comi, Giacomo P.
In: Journal of Neurology, Vol. 261, No. 1, 01.2014, p. 83-97.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Extended phenotype description and new molecular findings in late onset glycogen storage disease type II
T2 - A northern Italy population study and review of the literature
AU - Remiche, Gauthier
AU - Ronchi, Dario
AU - Magri, Francesca
AU - Lamperti, Costanza
AU - Bordoni, Andreina
AU - Moggio, Maurizio
AU - Bresolin, Nereo
AU - Comi, Giacomo P.
PY - 2014/1
Y1 - 2014/1
N2 - Glycogen storage disease type II (GSDII) is a lysosomal storage disorder caused by acid alpha-1,4-glucosidase deficiency and associated with recessive mutations in its coding gene GAA. Few studies have provided so far a detailed phenotypical characterization in late onset GSDII (LO-GSDII) patients. Genotype-phenotype correlation has been previously attempted with controversial results. We aim to provide an in-depth description of a cohort (n = 36) of LO-GSDII patients coming from the north of Italy and compare our population's findings to the literature. We performed a clinical record-based retrospective and prospective study of our patients. LO-GSDII in our cohort covers a large variability of phenotype including subtle clinical presentation and did not differ significantly from previous data. In all patients, molecular analysis disclosed GAA mutations, five of them being novel. To assess potential genotype-phenotype correlations we divided IVS1-32-13T>G heterozygous patients into two groups following the severity of the mutations on the second allele. Our patients harbouring "severe" mutations (n = 21) presented a strong tendency to have more severe phenotypes and more disability, more severe phenotypes and more disability, higher prevalence of assisted ventilation and a shorter time of evolution to show it. The determination of prognostic factors is mandatory in order to refine the accuracy of prognostic information, to develop follow-up strategy and, more importantly, to improve the decision algorithm for enzyme replacement therapy administration. The demonstration of genotype-phenotype correlations could help to reach this objective. Clinical assessment homogeneity is required to overcome limitations due to the lack of power of most studies.
AB - Glycogen storage disease type II (GSDII) is a lysosomal storage disorder caused by acid alpha-1,4-glucosidase deficiency and associated with recessive mutations in its coding gene GAA. Few studies have provided so far a detailed phenotypical characterization in late onset GSDII (LO-GSDII) patients. Genotype-phenotype correlation has been previously attempted with controversial results. We aim to provide an in-depth description of a cohort (n = 36) of LO-GSDII patients coming from the north of Italy and compare our population's findings to the literature. We performed a clinical record-based retrospective and prospective study of our patients. LO-GSDII in our cohort covers a large variability of phenotype including subtle clinical presentation and did not differ significantly from previous data. In all patients, molecular analysis disclosed GAA mutations, five of them being novel. To assess potential genotype-phenotype correlations we divided IVS1-32-13T>G heterozygous patients into two groups following the severity of the mutations on the second allele. Our patients harbouring "severe" mutations (n = 21) presented a strong tendency to have more severe phenotypes and more disability, more severe phenotypes and more disability, higher prevalence of assisted ventilation and a shorter time of evolution to show it. The determination of prognostic factors is mandatory in order to refine the accuracy of prognostic information, to develop follow-up strategy and, more importantly, to improve the decision algorithm for enzyme replacement therapy administration. The demonstration of genotype-phenotype correlations could help to reach this objective. Clinical assessment homogeneity is required to overcome limitations due to the lack of power of most studies.
KW - Correlation
KW - Genotype
KW - Glycogen storage disease type II (GSDII)
KW - Phenotype
KW - Prognosis
KW - Review
UR - http://www.scopus.com/inward/record.url?scp=84895076399&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84895076399&partnerID=8YFLogxK
U2 - 10.1007/s00415-013-7137-2
DO - 10.1007/s00415-013-7137-2
M3 - Article
C2 - 24158270
AN - SCOPUS:84895076399
VL - 261
SP - 83
EP - 97
JO - Journal of Neurology
JF - Journal of Neurology
SN - 0340-5354
IS - 1
ER -