Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
590
result(s) for
"Glycogen Storage Disease Type II"
Sort by:
Enzyme therapy and immune response in relation to CRIM status: the Dutch experience in classic infantile Pompe disease
Background
Enzyme-replacement therapy (ERT) in Pompe disease—an inherited metabolic disorder caused by acid α-glucosidase deficiency and characterized in infants by generalized muscle weakness and cardiomyopathy—can be complicated by immune responses. Infants that do not produce any endogenous acid α-glucosidase, so-called CRIM-negative patients, reportedly develop a strong response. We report the clinical outcome of our Dutch infants in relation to their CRIM status and immune response.
Methods
Eleven patients were genotyped and their CRIM status was determined. Antibody formation and clinical outcome were assessed for a minimum of 4 years.
Results
ERT was commenced between 0.1 and 8.3 months of age, and patients were treated from 0.3 to 13.7 years. All patients developed antibodies. Those with a high antibody titer (above 1:31,250) had a poor response. The antibody titers varied substantially between patients and did not strictly correlate with the patients’ CRIM status. Patients who started ERT beyond 2 months of age tended to develop higher titers than those who started earlier. All three CRIM-negative patients in our study succumbed by the age of 4 years seemingly unrelated to the height of their antibody titer.
Conclusion
Antibody formation is a common response to ERT in classic infantile Pompe disease and counteracts the effect of treatment. The counteracting effect seems determined by the antibody:enzyme molecular stoichiometry. The immune response may be minimized by early start of ERT and by immune modulation, as proposed by colleagues. The CRIM-negative status itself seems associated with poor outcome.
Journal Article
CRIM-negative infantile Pompe disease: characterization of immune responses in patients treated with ERT monotherapy
Purpose:
Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) prolongs survival in infantile Pompe disease (IPD). However, the majority of cross-reactive immunologic material (CRIM)–negative (CN) patients have immune responses with significant clinical decline despite continued ERT. We aimed to characterize immune responses in CN patients with IPD receiving ERT monotherapy.
Methods:
A chart review identified 20 CN patients with IPD treated with ERT monotherapy for ≥6 months. Patients were stratified by anti-rhGAA antibody titers: high sustained antibody titers (HSAT; ≥51,200) at least twice; low titers (LT; <6,400) throughout treatment; or sustained intermediate titers (SIT; 6,400–25,600).
Results:
Despite early initiation of treatment, the majority (85%) of CN patients developed significant antibody titers, most with HSAT associated with invasive ventilation and death. Nearly all patients with HSAT had at least one nonsense
GAA
mutation, whereas the LT group exclusively carried splice-site or frameshift mutations. Only one patient in the HSAT group is currently alive after successful immune modulation in the entrenched setting.
Conclusion:
Immunological responses are a significant risk in CN IPD; thus induction of immune tolerance in the naive setting should strongly be considered. Further exploration of factors influencing immune responses is required, particularly with the advent of newborn screening for Pompe disease.
Genet Med
17
11, 912–918.
Journal Article
Pompe's disease
Pompe's disease, glycogen-storage disease type II, and acid maltase deficiency are alternative names for the same metabolic disorder. It is a pan-ethnic autosomal recessive trait characterised by acid α-glucosidase deficiency leading to lysosomal glycogen storage. Pompe's disease is also regarded as a muscular disorder, but the generalised storage of glycogen causes more than mobility and respiratory problems. The clinical spectrum is continuous and broad. First symptoms can present in infants, children, and adults. Cardiac hypertrophy is a key feature of classic infantile Pompe's disease. For a long time, there was no means to stop disease progression, but the approval of enzyme replacement therapy has substantially changed the prospects for patients. With this new development, the disease is now among the small but increasing number of lysosomal storage disorders, for which treatment has become a reality. This review is meant to raise general awareness, to present and discuss the latest insights in disease pathophysiology, and to draw attention to new developments about diagnosis and care. We also discuss the developments that led to the approval of enzyme replacement therapy with recombinant human α-glucosidase from Chinese hamster ovary cells (alglucosidase alfa) by the US Food and Drug Administration and European Medicines Agency in 2006, and review clinical practice.
Journal Article
A cross-sectional single-centre study on the spectrum of Pompe disease, German patients: molecular analysis of the GAA gene, manifestation and genotype-phenotype correlations
Background
Pompe disease (Glycogen storage disease type II, GSD II, acid alpha-glucosidase deficiency, acid maltase deficiency, OMIM # 232300) is an autosomal-recessive lysosomal storage disorder due to a deficiency of acid alpha-glucosidase (GAA, acid maltase, EC 3.2.1.20, Swiss-Prot P10253). Clinical manifestations are dominated by progressive weakness of skeletal muscle throughout the clinical spectrum. In addition, the classic infantile form is characterised by hypertrophic cardiomyopathy.
Methods
In a cross-sectional single-centre study we clinically assessed 3 patients with classic infantile Pompe disease and 39 patients with non-classic presentations, measured their acid alpha-glucosidase activities and analysed their GAA genes.
Results
Classic infantile patients had nearly absent residual enzyme activities and a typical clinical course with hypertrophic cardiomyopathy until the beginning of therapy. The disease manifestations in non-classic patients were heterogeneous. There was a broad variability in the decline of locomotive and respiratory function. The age of onset ranged from birth to late adulthood and correlated with enzyme activities. Molecular analysis revealed as many as 33 different mutations, 14 of which are novel. All classic infantile patients had two severe mutations. The most common mutation in the non-classic group was c.-32-13 T > G. It was associated with a milder course in this subgroup.
Conclusions
Disease manifestation strongly correlates with the nature of the GAA mutations, while the variable progression in non-classic Pompe disease is likely to be explained by yet unknown modifying factors. This study provides the first comprehensive dataset on the clinical course and the mutational spectrum of Pompe disease in Germany.
Journal Article
Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study
Background
Due 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.
Methods
We 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.
Results
Between 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.
Conclusions
Recognizing 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.
Journal Article
Newborn screening for Pompe disease in Japan: report and literature review of mutations in the GAA gene in Japanese and Asian patients
A newborn screening program for Pompe disease using dried blood spots (DBSs) was initiated in Japan. Here, we summarized this screening program and described the results of the GAA gene analysis. From April 2013 to November 2016, 103,204 newborns were screened; 71 had low acid alpha-glucosidase (AαGlu) activity. GAA sequencing showed that 32 (45.1%) and 37 (52.1%) of these newborns were homozygous and heterozygous for pseudodeficiency alleles c.[1726G>A; 2965G>A], respectively. Moreover, 24 of 32 newborns with homozygous c.[1726G>A; 2965G>A] alleles had no mutations, and the other eight had one mutation each. Thirty-five of 37 newborns with heterozygous c.[1726G>A; 2965G>A] alleles had one mutation, and the other two had two mutations each. Only one newborn who had two mutations did not harbor c.[1726G>A; 2965G>A] alleles. Thus, it was difficult to distinguish newborns with c.[1726G>A; 2965G>A] alleles from newborns with pre-symptomatic Pompe disease using AαGlu assays in DBSs or fibroblasts; GAA gene sequencing was necessary. Seventy-one newborns had 50 variants, including 21 mutations or predictably pathogenic variants, and 29 polymorphisms or predictably non-pathogenic variants. Four of 21 mutations or predictably pathogenic variants and four of 29 polymorphisms or predictably non-pathogenic variants were novel. No infantile-onset Pompe disease was detected, and three newborns were diagnosed with potential late-onset Pompe disease. In the literature, 156 variants have been reported for 296 patients from 277 families in 41 articles from Japan, Korea, Taiwan, and China. Our results provide insights into GAA gene mutation profiles and the relationship between GAA and Pompe disease in Asian populations.
Journal Article
Late-onset Pompe disease (LOPD) in Belgium: clinical characteristics and outcome measures
Background
Late-onset Pompe disease (LOPD) is a rare, hereditary, progressive disorder that is usually characterized by limb-girdle muscle weakness and/or respiratory insufficiency. LOPD is caused by mutations in the acid alpha-glucosidase (
GAA
) gene and treated with enzyme replacement therapy (ERT).
Methods
We studied the clinical, brain imaging, and genetic features of the Belgian cohort of late-onset Pompe disease patients (
N
= 52), and explored the sensitivity of different outcome measures, during a longitudinal period of 7 years (2010–2017), including the activity limitations ActivLim score, 6 min walking distance (6MWD), 10 m walk test (10MWT), MRC sum score, and forced vital capacity (FVC) sitting/supine.
Results
In Belgium, we calculated an LOPD prevalence of 3.9 per million. Mean age at onset of 52 LOPD patients was 28.9 years (SD: 15.8 y), ranging from 7 months to 68 years. Seventy-five percent (
N
= 39) of the patients initially presented with limb-girdle weakness, whereas in 13% (
N
= 7) respiratory symptoms were the only initial symptom. Non-invasive ventilation (NIV) was started in 37% (
N
= 19), at a mean age of 49.5 years (SD: 11.9 y), with a mean duration of 15 years (SD: 10.2 y) after symptom onset. Brain imaging revealed abnormalities in 25% (
N
= 8) of the patients, with the presence of small cerebral aneurysm(s) in two patients and a vertebrobasilar dolichoectasia in another two. Mean diagnostic delay was 12.9 years. All patients were compound heterozygotes with the most prevalent mutation being c.-32-13 T > G in 96%. We identified two novel mutations in
GAA
: c.1610_1611delA and c.186dup11. For the 6MWD, MRC sum score, FVC sitting and FVC supine, we measured a significant decrease over time (
p
= 0.0002,
p
= 0.0001,
p
= 0.0077,
p
= 0.0151), which was not revealed with the ActivLim score and 10MWT (
p
> 0.05).
Conclusions
Awareness on LOPD should even be further increased because of the long diagnostic delay. The 6MWD, but not the ActivLim score, is a sensitive outcome measure to follow up LOPD patients.
Journal Article
Global variations in diagnostic methods and epidemiological estimates in Pompe disease: findings from a scoping review
Background
Pompe disease is caused by pathogenic variants in the
GAA
gene, resulting in lysosomal acid α-glucosidase (GAA) deficiency. The prevalence of Pompe disease is not well-defined, and estimates vary by geographic region. We evaluated the global epidemiology of Pompe disease and the potential reasons for differing prevalence estimates using published data from worldwide newborn screening (NBS) programs and population-based studies.
Methods
A comprehensive literature search in PubMed was conducted in July 2023, updated in March 2024, and validated with an Embase search in June 2024. Search terms included Pompe disease, GSDII, prevalence, incidence, epidemiology, survival, mortality, and NBS. Studies were included based on robust epidemiological methods, the presence of disease definition, and publication within the past 5 years. We identified 1210 abstracts, of which 295 met recency criteria, 30 were deemed relevant, and 11 met all inclusion criteria.
Results
Prevalence estimates and GAA enzyme activity cutoff values varied across geographic regions. In NBS studies, the birth prevalence of infantile-onset Pompe disease (IOPD) ranged from 1 in 297,387 in Japan to 1 in 62,186 in Taiwan, and late-onset Pompe disease (LOPD) ranged from 1 in 82,914 in Taiwan to 1 in 17,133 in Pennsylvania. Data from the French National Pompe Registry (N = 246) showed an increase in diagnosis of LOPD from 2.6/year before 2001 to 10.6/year during 2001–2010 and 12.8/year during 2011–2015. Enzyme cutoffs in dried blood spots varied from < 3% of lymphocyte mean to 2.10 μmol/L/h to ≤ 18% of the daily median. Three studies noted higher prevalence in populations of African descent, and two noted a higher frequency of pseudodeficiency alleles in Asian populations.
Conclusions
This scoping review confirmed that prevalence estimates differ for IOPD and LOPD and vary by geographic region, potentially by race and ethnicity. It highlights the need to standardize screening and diagnosis methods, genetic testing protocols, and uniform disease classification between IOPD and LOPD.
Journal Article