Adult Pompe disease: Clinical manifestations and outcome of the first Greek patients receiving enzyme replacement therapy

Papadimas, Georgios; Spengos, Konstantinos; Konstantinopoulou, A.; Vassilopoulou, Sofia; Vontzalidis, Adamantios; Papadopoulos, Constantinos; Michelakakis, Helen; Manta, Panagiota

doi:10.1016/j.clineuro.2010.12.005

Cited by 23 publications

(17 citation statements)

References 20 publications

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“…The substantial differences in age of symptom onset observed in the 12 families with an identical GAA genotype (c.-32-13 T > G/c.525delT (r.0)) suggest that other factors such as variability in genetic background, modifying genes or environmental factors are likely to play a role [5,8,14,16,20,30]. An example of a potential modifying gene is the angiotensin-converting enzyme gene, which has been described as playing a role in modulating phenotype and prognosis in Pompe disease [31,32].…”

Section: Discussionmentioning

confidence: 99%

Phenotypical variation within 22 families with Pompe disease

Wens

Gelder

Kruijshaar

et al. 2013

Orphanet Journal of Rare Diseases

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BackgroundPompe disease has a broad clinical spectrum, in which the phenotype is partially explained by the genotype. The aim of this study was to describe phenotypical variation among siblings with non-classic Pompe disease. We hypothesized that siblings and families with the same genotype share more similar phenotypes than the total population of non-classic Pompe patients, and that this might reveal genotype-phenotype correlations.MethodsWe identified all Dutch families in which two or three siblings were diagnosed with Pompe disease and described genotype, acid α-glucosidase activity, age at symptom onset, presenting symptoms, specific clinical features, mobility and ventilator dependency.ResultsWe identified 22 families comprising two or three siblings. All carried the most common mutation c.-32-13 T > G in combination with another pathogenic mutation. The median age at symptom onset was 33 years (range 1–62 years). Within sibships symptom onset was either in childhood or in adulthood. The median variation in symptom onset between siblings was nine years (range 0–31 years). Presenting symptoms were similar across siblings in 14 out of 22 families. Limb girdle weakness was most frequently reported. In some families ptosis or bulbar weakness were present in all siblings. A large variation in disease severity (based on wheelchair/ventilator dependency) was observed in 11 families. This variation did not always result from a difference in duration of the disease since a third of the less affected siblings had a longer course of the disease. Enzyme activity could not explain this variation either. In most families male patients were more severely affected. Finally, symptom onset varied substantially in twelve families despite the same GAA genotype.ConclusionIn most families with non-classic Pompe disease siblings share a similar phenotype regarding symptom onset, presenting symptoms and specific clinical features. However, in some families the course and severity of disease varied substantially. This phenotypical variation was also observed in families with identical GAA genotypes. The commonalities and differences indicate that besides genotype, other factors such as epigenetic and environmental effects influence the clinical presentation and disease course.

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Section: Discussionmentioning

confidence: 99%

Phenotypical variation within 22 families with Pompe disease

Wens

Gelder

Kruijshaar

et al. 2013

Orphanet Journal of Rare Diseases

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“…FVC was measured in five patients from one study who were tested after 4 to 5 years of ERT (Deroma et al 2014). case report 1 (Winkel et al 2004) was reported as improved after 3 years of ERT from 14% (value not reported, reported here as 15%); measurements illustrated here for case reports 3 and 4 (Orlikowski et al 2011) and 11 (Papadimas et al 2011) were taken in the sitting position; case report 7 (Ishigaki et al 2012) improved after 4 months ERT from 57 to 65% but was reported to return to baseline after 18 months (no value given, reported here as 57%); Korpel et al (2009) case showed no improvement after 6 months ERT from 26% at baseline (value not reported). Case notes B: data for case reports 6 and 7 (Furusawa et al 2012) were rounded to the nearest whole number for the purpose of reporting here FVC scores over 80% are considered to be within the normal range (Lachmann and Schoser 2013), so at baseline, three of the five patients were considered to have normal respiratory functioning.…”

Section: Cardiorespiratory Functionmentioning

confidence: 99%

“…VC was measured in seven case reports, two of which (Orlikowski et al 2011;Papadimas et al 2011) reported readings in the sitting and supine positions. Measurements taken at 4 to 6 months from baseline showed an increase in VC and FVC, with one exception in a patient whose VC remained unchanged while receiving ERT (Orlikowski et al 2011).…”

Section: Cardiorespiratory Functionmentioning

confidence: 99%

The effectiveness of enzyme replacement therapy for juvenile-onset Pompe disease: a systematic review

Milverton

Newton

Merlin

2018

J Inherit Metab Dis

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Aim The objective of this research was to determine the effectiveness of enzyme replacement therapy for juvenile-onset Pompe disease (patients aged 2 to 18 years at symptom onset) by systematic review. Methods A systematic search was conducted according to a protocol designed a priori of bibliographic databases and search engines. Studies selected according to pre-specified criteria were assessed for quality and risk of bias using standardised appraisal tools. Data were reported according to PRISMA conventions (Liberati et al. in PLoS Med 6:e1000100, 2009) and synthesised using GRADE (Guyatt et al. in J Clin Epidemiol 64:380-382, 2011). Results Of 2537 titles screened, 1 case series and 16 case reports met the inclusion criteria. No studies reported on the impact of enzyme replacement therapy on the survival of juvenile-onset patients. Low level evidence found that respiratory function may improve or be maintained in the early months of therapy. Improved muscle function in the first 6 to 12 months was also suggested, but results may be confounded by natural development. Patients with less severe baseline status and treated at a younger age showed more response than patients with more severe baseline status, treated as adults. Conclusions Interpretation of the findings was hindered by the lack of good quality evidence. The available data suggests that some JOPD patients may benefit in the short term from ERT through improved muscle strength and a reduced need for assisted ventilation. A focus by clinicians on improved and more consistent evidence collection, and use of study designs tailored to rare conditions, would provide more definitive results.

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“…Three pairs of siblings, that have been previously reported [6], [7], are presented. With the exception of the male sibling of pair 3 who was not followed in our center, and to whom clinical details were obtained from his sister, all other patients were analyzed retrospectively.…”

Section: Methods and Resultsmentioning

confidence: 99%

Highlighting intrafamilial clinical heterogeneity in late-onset Pompe disease

Papadopoulos

Papadimas

Michelakakis

et al. 2014

Molecular Genetics and Metabolism Reports

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Background/aimsPompe disease is a rare metabolic disorder caused by deficiency of the lysosomal enzyme acid alpha-glycosidase (GAA). The late onset form of the disease is characterized by muscle weakness and respiratory involvement of variable severity. The aim of this short communication is to highlight the clinical variability of Pompe disease within siblings suffering from the disease.Case reportsWe report three pairs of siblings with late-onset Pompe disease presenting with different clinical phenotypes within the spectrum of disease phenotypes.ConclusionClinical manifestations in Pompe disease within the same family can be very different. Clinicians should investigate patients' siblings for symptoms throughout the entire spectrum of the disease in order to avoid delays in the diagnosis and to pick-up mildly affected persons as early as possible, when they can benefit the most from enzyme replacement therapy.

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Adult Pompe disease: Clinical manifestations and outcome of the first Greek patients receiving enzyme replacement therapy

Cited by 23 publications

References 20 publications

Phenotypical variation within 22 families with Pompe disease

Phenotypical variation within 22 families with Pompe disease

The effectiveness of enzyme replacement therapy for juvenile-onset Pompe disease: a systematic review

Highlighting intrafamilial clinical heterogeneity in late-onset Pompe disease

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