Detection of Pompe Disease in Adult Patients With Myopathies of Uncertain Origin or With Asymptomatic Hyper-CK-emia
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| ClinicalTrials.gov Identifier: NCT01482494 |
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Recruitment Status
: Unknown
Verified November 2011 by Jordi Perez Lopez, Hospital Vall d'Hebron.
Recruitment status was: Not yet recruiting
First Posted
: November 30, 2011
Last Update Posted
: December 1, 2011
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The adult onset form can occur between the second and sixth decades of life as a form of proximal myopathy, predominantly in the pelvic girdle area. Sometimes the first symptoms are shortness of breath and diaphragm weakness which herald progressive proximal muscle weakness. The heart and liver are not affected.
Serum CK (Creatine Kinase) activity is 2 to 10 times higher than normal. EMG (electromyogram) testing usually reveals a myopathic pattern and muscle biopsy may show vacuoles containing an accumulation of glycogen that is not broken down.
Until fairly recently, an assay of acid maltase activity using cultured fibroblasts after biopsy of skin or muscle tissue was required for diagnosis, as leukocytes contain a renal isoenzyme that is not absent in these patients and which can mask the deficit and result in false negatives. In recent years this problem has ben solved by the introduction of acarbose, an inhibitor of renal α-glucosidase; it is also used in the dried blood spot method, which measures acid maltase activity using maltose and acarbose as inhibitors and 4-methylumbelliferyl-D-glucopyranoside as substrate.
| Condition or disease |
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| Pompe Disease |
Lysosomal storage disorders are inborn errors of metabolism characterized by defects in lysosomal function. Lysosomes contain acid hydrolases whose function is to break down complex molecules in the cell into simpler ones. A deficiency in the activity of any of these enzymes results in the progressive accumulation of substances that cause a storage disease.
Pompe disease is a progressive muscle disease that is often fatal, caused by a deficiency of lysosomal alpha glucosidase (also known as acid maltase) activity. This leads to the accumulation of glycogen in many tissues, most notably in skeletal and cardiac tissues and in muscle tissue. It is therefore also a glycogen storage disease (type II).
It is inherited in an autosomal recessive manner and was the first lysosomal storage disease to be identified. The incidence rate varies by geographic area and ethnic group, and is estimated to be between 1/300,000 to 1:40,000.
It has a broad clinical spectrum that varies with respect to age of onset, rate of progression and extent of organ involvement.
The adult onset form can occur between the second and sixth decades of life as a form of proximal myopathy, predominantly in the pelvic girdle area. Sometimes the first symptoms are shortness of breath and diaphragm weakness which herald progressive proximal muscle weakness. The heart and liver are not affected.
Serum CK (Creatine Kinase) activity is 2 to 10 times higher than normal. EMG (electromyogram) testing usually reveals a myopathic pattern and muscle biopsy may show vacuoles containing an accumulation of glycogen that is not broken down.
Until fairly recently, an assay of acid maltase activity using cultured fibroblasts after biopsy of skin or muscle tissue was required for diagnosis, as leukocytes contain a renal isoenzyme that is not absent in these patients and which can mask the deficit and result in false negatives. In recent years this problem has ben solved by the introduction of acarbose, an inhibitor of renal α-glucosidase; it is also used in the dried blood spot method, which measures acid maltase activity using maltose and acarbose as inhibitors and 4-methylumbelliferyl-D-glucopyranoside as substrate.
Diagnosis is based on clinical suspicion, determination of lysosomal acid alpha-glucosidase activity and confirmation of a mutation in the gene for this enzyme, located on chromosome 17.
Glycogenosis type II is a multisystem disorder and therefore requires a multidisciplinary approach for its treatment. Motor recovery, ventilatory support and nutritional management in patients with gastrointestinal involvement, are seen as fundamental to the treatment. Since 2.000, enzyme replacement therapy with alpha-alglucosidase has been used, whose safety and effectiveness, especially in childhood, has been published in several papers.
| Study Type : | Observational |
| Estimated Enrollment : | 50 participants |
| Official Title: | Detection of Pompe Disease in Adult Patients With Myopathies of Uncertain Origin or With Asymptomatic Hyper-CK-emia |
| Study Start Date : | December 2011 |
| Estimated Primary Completion Date : | December 2012 |
| Group/Cohort |
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Pompe suspected patients
Patients who go to an Internal Medicine clinic for examination of a limb-girdle myopathy. Patients with asymptomatic hyper-CK-emia. Patients with a prior diagnosis of polymyositis. Patients with a myopathy of uncertain origin and respiratory insufficiency. Patients with polymyositis unresponsive to steroid therapy |
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| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Probability Sample |
Prospectively, patients who go to an Internal Medicine clinic for suspected limb-girdle myopathy or patients with asymptomatic hyper-CK-emia shall be included.
Retrospectively, patients with a prior diagnosis of polymyositis and patients with a myopathy of uncertain origin accompanied by respiratory insufficiency shall be included.
Before being included in the study, all patients will be asked to give informed consent.
Acid maltase activity shall be determined by tests performed on leukocytes obtained from peripheral blood samples (5 mL).
Inclusion Criteria:
Patients who go to an Internal Medicine clinic for examination of a limb-girdle myopathy.
Patients with asymptomatic hyper-CK-emia. Patients with a prior diagnosis of polymyositis. Patients with a myopathy of uncertain origin and respiratory insufficiency. Patients with polymyositis unresponsive to steroid therapy
Exclusion Criteria:
Patients in treatment Patients with Pompe Disease
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01482494
| Spain | |
| Hospital Clínico de Barcelona | Not yet recruiting |
| Barcelona, Spain | |
| Responsible Party: | Jordi Perez Lopez, Médico Adjunto especialista en Medicina Interna.Responsable de la Unidad de Enfermedades Minoritarias, Hospital Vall d'Hebron |
| ClinicalTrials.gov Identifier: | NCT01482494 History of Changes |
| Other Study ID Numbers: |
GZ-2011-10784 |
| First Posted: | November 30, 2011 Key Record Dates |
| Last Update Posted: | December 1, 2011 |
| Last Verified: | November 2011 |
Keywords provided by Jordi Perez Lopez, Hospital Vall d'Hebron:
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Myopathies Pompe disease Polymyositis Respiratory Insufficiency |
Additional relevant MeSH terms:
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Muscular Diseases Glycogen Storage Disease Type II Musculoskeletal Diseases Neuromuscular Diseases Nervous System Diseases Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic |
Brain Diseases Central Nervous System Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Glycogen Storage Disease Carbohydrate Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases |