scholarly journals Homozygotic intronic GAA mutation in three siblings with late-onset Pompe's disease

2010 ◽  
Vol 68 (2) ◽  
pp. 194-197 ◽  
Author(s):  
Anderson Kuntz Grzesiuk ◽  
Sueli Mieko Oba Shinjo ◽  
Roseli da Silva ◽  
Marcela Machado ◽  
Marcial Francis Galera ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Age Of Onset ◽  
Late Onset ◽  
Activity Measurement ◽  
Respiratory Compromise ◽  
Enzyme Replacement ◽  
Pompe’S Disease ◽  
Pompe's Disease ◽  
C 32 ◽  
Gaa Gene

Pompe's disease (PD) is a metabolic myopathy caused by the accumulation of lysosomal glycogen, secondary to acid α-glucosidase (GAA) enzyme deficiency. Childhood and late-onset forms are described, differing by the age of onset and symptoms. In this study were analyzed affected siblings with Pompe's disease (PD) and their distinct clinical and pathological presentations. METHOD: Diagnosis was performed by the clinical presentation of limb-girdle dystrophies and respiratory compromise. Confirmatory diagnoses were conducted by muscle biopsy, GAA activity measurement and by GAA gene genotyping. RESULTS: The findings suggested muscular involvement due to GAA deficiency. GAA genotyping showed they are homozygous for the c.-32-3C>A mutation. CONCLUSION: Herein we reported a family where three out of five siblings were diagnosed with late-onset PD, although it is a rare metabolic disease inherited in an autossomal recessive manner. We emphasize the importance of including this presentation within the differential diagnoses of the limb-girdle dystrophies once enzyme replacement therapy is available.

scholarly journals Clinical Analysis of Algerian Patients with Pompe Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Y. Sifi ◽  
M. Medjroubi ◽  
R. Froissart ◽  
N. Taghane ◽  
K. Sifi ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Pompe Disease ◽  
Clinical Presentation ◽  
Age Of Onset ◽  
Late Onset ◽  
Disease Onset ◽  
Dried Blood Spots ◽  
Clinical Analysis ◽  
Pompe’S Disease ◽  
Pompe's Disease

Pompe’s disease is a metabolic myopathy caused by a deficiency of acid alpha-glucosidase (GAA), also called acid maltase, an enzyme that degrades lysosomal glycogen. The clinical presentation of Pompe’s disease is variable with respect to the age of onset and rate of disease progression. Patients with onset of symptoms in early infancy (infantile-onset Pompe disease (IOPD)) typically exhibit rapidly progressive hypertrophic cardiomyopathy and marked muscle weakness. Most of them die within the first year of life from cardiac and/or respiratory failure. In the majority of cases of Pompe’s disease, onset of symptoms occurs after infancy, ranging widely from the first to sixth decade of life (late-onset Pompe’s disease or LOPD). Progression of the disease is relentless and patients eventually progress to loss of ambulation and death due to respiratory failure. The objective of this study was to characterize the clinical presentation of 6 patients (3 with EOPD and the other 3 with LOPD) of 5 families from the East of Algeria. All our patients were diagnosed as having Pompe’s disease based on biochemical confirmations of GAA deficiency by dried blood spots (DBS) and GAA gene mutations were analyzed in all patients who consented (n=4). Our results are similar to other ethnic groups.

scholarly journals Rare Diseases in Neurology — Caring for a Patient with Pompe’s Disease

2019 ◽  
Vol 8 (4) ◽  
pp. 170-176
Author(s):  
Anna Roszmann ◽  
◽  
Mikołaj Hamerski ◽  
Marcelina Skrzypek-Czerko ◽  
◽  
...  
Keyword(s):  
Clinical Picture ◽  
Pompe Disease ◽  
Age Of Onset ◽  
Late Onset ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Pompe’S Disease ◽  
Pompe's Disease ◽  
Disease Case ◽  
Nurses Role

Introduction. Pompe disease, a severe metabolic myopathy, is caused by mutations in the gene coding for acid alphaglucosidase (GAA), what lead to intralysosomal accumulation of glycogen in all tissues, most notably in skeletal muscles. Pompe disease was the first documented lysosomal storage disease, nowadays we know around 60 similar disorders. Aim. Presentation of the clinical picture of a man with Pompe’s disease. Case Report. A man at the age of 40, diagnosis of the Pompe’s disease was made only at the age of 31. The first symptoms, indicating the patient’s development of the disease, were already present in the early school age. At first, the clinical picture presented by the patient led to the diagnosis of muscular dystrophy. Discussion. Pompe disease presents as a continuum of clinical phenotypes that differ by age of onset, severity, and organ involvement. Pompe disease affects people of all ages with varying degrees of severity. Two main broad types are recognized based on the onset of symptoms and the presence or absence of cardiomyopathy. Infantile onset Pompe disease (IOPD) as one, and the most severe for mod the disease. Other and less destructive is late-onset Pompe disease (LOPD) manifests any time after 12 months of age. The disease can be successfully treated by enzyme replacement therapy with alglucosidase alfa that was approved for human use in 2006. Conclusions. In big importance is nurses role as educators and support for the patients during their hospitalizations for medicine infusions twice a month. It time when the knowledge and significance of proper life style can be discussed and implemented to empower the patients. (JNNN 2019;8(4):170–176) Key Words: Pompe’s disease, treatment, diagnosis, care

scholarly journals Clinical manifestation, disease course and response to enzyme replacement therapy in Hungarian patients with Pompe’s disease

2011 ◽  
Vol 152 (39) ◽  
pp. 1569-1575
Author(s):  
Benjamin Bereznai ◽  
Anita Trauninger ◽  
Ilona György ◽  
Katalin Szakszon ◽  
Zsuzsanna Almássy ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Age Of Onset ◽  
Late Onset ◽  
Phenotypic Variability ◽  
Motor Deficits ◽  
Enzyme Replacement ◽  
Pompe’S Disease ◽  
Pompe's Disease ◽  
Long Term Follow Up

Pompe’s disease is an autosomal recessive disease caused by deficiency of acid-alpha-glucosidase. Aims and Methods: Authors analyzed the phenotype of 11 Hungarian patients with Pompe’s disease and evaluated clinical parameters and response to enzyme replacement therapy during a long-term follow-up in 8 patients. Results: One patient with atypical infantile form presented with cardiomyopathy and a very slow progression of motor deficits; after 2 years of enzyme replacement therapy no disability was present at the age 6 years. Another patient was asymptomatic at the age of 2.5 years. The adult onset form was characterized by slight to prominent limb-girdle myopathy with an age of onset between 20 and 50 years. In 3 of such cases respiratory insufficiency was also present. Conclusions: Hungarian patients with Pompe’s disease presented with a wide phenotypic variability ranging from atypical early childhood form with slowly progressive course to late-onset limb-girdle myopathy with variable courses. Enzyme replacement therapy resulted in significant improvement in motor and respiratory functions in most of the patients. Orv. Hetil., 2011, 152, 1569–1575.

scholarly journals Pompe disease, a storage cardiomyopathy

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Tiziana Felice
Keyword(s):  
Pompe Disease ◽  
Age Of Onset ◽  
Late Onset ◽  
Treatment Options ◽  
Premature Death ◽  
Glycogen Storage Disease Type ◽  
Lysosomal Storage ◽  
Respiratory Compromise ◽  
Enzyme Replacement ◽  
Geographical Regions

Pompe disease also known as glycogen storage disease type II, is a rare and progressive lysosomal storage disorder caused by the deficiency of the enzyme acid α-glucosidase. This results in the accumulation of glycogen in various tissues particularly involving the heart, skeletal muscle and liver. It is inherited in an autosomal recessive manner due to mutations in the GAA gene. There are several known pathogenic variants, some of which are particularly common in certain geographical regions. Pompe disease is a single disease exhibiting a heterogeneous clinical spectrum depending on the extent of enzyme deficiency, the age of onset, the progression of the disease and the degree of organ involvement. It may lead to muscle weakness, hypotonia, respiratory compromise and premature death. Pompe disease is classically divided into two forms, infantile and late-onset disease. The infantile form is further subdivided into classical and non-classical subtypes. Cardiac involvement is particularly seen in the infantile phenotype of the condition, presenting as severe cardiomyopathy associated with conduction abnormalities. Enzyme replacement therapy with recombinant human acid α-glucosidase is the approved treatment option for patients with this metabolic condition. Further research is currently being done to explore more treatment options. One must keep in mind other metabolic and mitochondrial conditions, which may give a similar cardiac and neurological clinical picture.

Enzyme replacement therapy in late-onset Pompe's disease: A three-year follow-up

2004 ◽  
Vol 55 (4) ◽  
pp. 495-502 ◽  
Author(s):  
L�on P. F. Winkel ◽  
Johanna M. P. Van den Hout ◽  
Joep H. J. Kamphoven ◽  
Janus A. M. Disseldorp ◽  
Maaike Remmerswaal ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Late Onset ◽  
Enzyme Replacement ◽  
Pompe’S Disease ◽  
Pompe's Disease

scholarly journals Correlation of GAA Genotype and Acid-α-Glucosidase Enzyme Activity in Hungarian Patients with Pompe Disease

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 507
Author(s):  
Aniko Gal ◽  
Zoltán Grosz ◽  
Beata Borsos ◽  
Ildikó Szatmari ◽  
Agnes Sebők ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Pompe Disease ◽  
Late Onset ◽  
Common Finding ◽  
Compound Heterozygous ◽  
Gene Variation ◽  
Enzyme Replacement ◽  
C 32 ◽  
The Impact ◽  
Gaa Gene

Pompe disease is caused by the accumulation of glycogen in the lysosomes due to a deficiency of the lysosomal acid-α-glucosidase (GAA) enzyme. Depending on residual enzyme activity, the disease manifests two distinct phenotypes. In this study, we assess an enzymatic and genetic analysis of Hungarian patients with Pompe disease. Twenty-four patients diagnosed with Pompe disease were included. Enzyme activity of acid-α-glucosidase was measured by mass spectrometry. Sanger sequencing and an MLPA of the GAA gene were performed in all patients. Twenty (83.33%) patients were classified as having late-onset Pompe disease and four (16.66%) had infantile-onset Pompe disease. Fifteen different pathogenic GAA variants were detected. The most common finding was the c.-32-13 T > G splice site alteration. Comparing the α-glucosidase enzyme activity of homozygous cases to the compound heterozygous cases of the c.-32-13 T > G disease-causing variant, the mean GAA activity in homozygous cases was significantly higher. The lowest enzyme activity was found in cases where the c.-32-13 T > G variant was not present. The localization of the identified sequence variations in regions encoding the crucial protein domains of GAA correlates with severe effects on enzyme activity. A better understanding of the impact of pathogenic gene variations may help earlier initiation of enzyme replacement therapy (ERT) if subtle symptoms occur. Further information on the effect of GAA gene variation on the efficacy of treatment and the extent of immune response to ERT would be of importance for optimal disease management and designing effective treatment plans.

scholarly journals Late-Onset Glycogen Storage Disease Type II (Pompe’s Disease) with a Novel Mutation: A Malaysian Experience

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Hiew Fu Liong ◽  
Siti Aishah Abdul Wahab ◽  
Yusnita Yakob ◽  
Ngu Lock Hock ◽  
Wong Kum Thong ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Late Onset ◽  
Novel Mutation ◽  
High Protein Diet ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Enzyme Replacement ◽  
Pompe’S Disease ◽  
Pompe's Disease

Pompe’s disease (acid maltase deficiency, glycogen storage disease type II) is an autosomal recessive disorder caused by a deficiency of lysosomal acidα-1,4-glucosidase, resulting in excessive accumulation of glycogen in the lysosomes and cytoplasm of all tissues, most notably in skeletal muscles. We present a case of adult-onset Pompe’s disease with progressive proximal muscles weakness over 5 years and respiratory failure on admission, requiring prolonged mechanical ventilation. Electromyography showed evidence of myopathic process with small amplitudes, polyphasic motor unit action potentials, and presence of pseudomyotonic discharges. Muscle biopsy showed glycogen-containing vacuoles in the muscle fibers consistent with glycogen storage disease. Genetic analysis revealed two compound heterozygous mutations at c.444C>G (p.Tyr148*) in exon 2 and c.2238G>C (p.Trp746Cys) in exon 16, with the former being a novel mutation. This mutation has not been reported before, to our knowledge. The patient was treated with high protein diet during the admission and subsequently showed good clinical response to enzyme replacement therapy with survival now to the eighth year.Conclusion. In patients with late-onset adult Pompe’s disease, careful evaluation and early identification of the disease and its treatment with high protein diet and enzyme replacement therapy improve muscle function and have beneficial impact on long term survival.

G.P.8.03 Misleading muscle biopsies in late onset Pompe’s disease

2009 ◽  
Vol 19 (8-9) ◽  
pp. 591-592 ◽  
Author(s):  
A.L. Taratuto ◽  
A. Dubrovsky ◽  
J. Corderi
Keyword(s):  
Late Onset ◽  
Pompe’S Disease ◽  
Pompe's Disease ◽  
Muscle Biopsies
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