Biomarker for Pompe Disease (BioPompe) (BioPompe)

Biomarker for Pompe Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGI-CAL PROTOCOL

Development of a new MS-based biomarker for the early and sensitive diagnosis of Pompe disease from blood (plasma)

Study Overview

• Status: Withdrawn
• Conditions: Lung Disease; Cerebral Aneurysm; Macroglossia; Cardiac Diseases; Obstructive Sleep Apnoea; Muscular Weakness; Hepato-splenomegaly

Detailed Description

Pompe disease is a rare (estimated at 1 in every 40,000 births), inherited and often fatal disorder that disables the heart and muscles. It is caused by mutations in a gene that encodes an enzyme called alpha-glucosidase (GAA). Normally, the body uses GAA to break down glycogen, the long-term storage form of sugar, into glucose, which the body can utilize to gain energy. But in Pompe disease, mutations in the GAA gene reduce or completely eliminate the activity of this essential enzyme. Excessive amounts of glycogen accumulate everywhere in the body, but the cells of the heart and skeletal muscles are the most seriously affected. Re-searchers have identified up to 70 different mutations in the GAA gene that cause the symptoms of Pompe disease, which can vary widely in terms of age of onset and severity. The severity of the disease and the age of onset are related to the degree of enzyme deficiency.

Early onset (or infantile) Pompe disease is the result of complete or near complete deficiency of GAA. Symptoms begin in the first months of life, with feeding problems, poor weight gain, muscle weakness, floppiness, and head lag. Respiratory difficulties are often complicated by lung infections. The heart is grossly enlarged. More than half of all infants with Pompe disease also have enlarged tongues. Most babies with Pompe disease die from cardiac or respiratory complications before their first birthday.

Late onset (or juvenile/adult) Pompe disease is the result of a partial deficiency of GAA. The onset can be as early as the first decade of childhood or as late as the sixth decade of adulthood. The primary symptom is muscle weakness progressing to respiratory weakness and death from respiratory failure after a course lasting several years. The heart may be involved but it will not be grossly enlarged. A diagnosis of Pompe disease can be confirmed by screening for the common genetic mutations or measuring the level of GAA enzyme activity in a blood sample - a test that has 100 percent accuracy. Once Pompe disease is diagnosed, testing of all family members and consultation with a professional geneticist is recommended. Carriers are most reliably identified via genetic mutation analysis.

New methods, like mass-spectrometry give a good chance to characterize in the blood (plasma) of affected patents specific metabolic alterations that allow to diagnose in the future the disease earlier, with a higher sensitivity and specificity.

Therefore it is the goal of the study to develop new biochemical markers from the plasma of the affected patients helping to benefit the patient by an early diagnose and thereby with an earlier treatment.

• Study Type: Observational

Contacts and Locations

Study Locations

• Germany
  • Rostock, Germany, 18055
    • Centogene AG
• India
  • Mumbai, India, 400705
    • Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN)
  • Kerala
    • Cochin, Kerala, India, 682041
      • Amrita Institute Of Medical Sciences & Research Centre
• Sri Lanka
  • Colombo 8, Sri Lanka, 00800c
    • Lady Ridgeway Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with Pompe disease

Description

Inclusion Criteria:

• Informed consent will be obtained from the patient or the parents before any study related procedures.
• Patients older than 12 months
• The patient has a diagnosis of Pompe disease

Exclusion Criteria:

• No Informed consent from the patient or the parents before any study related procedures
• Patients younger than 12 months
• The patient has no diagnosis of Pompe disease

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Observation; Patients with Pompe disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of a new MS-based biomarker for the early and sensitive diagnosis of Pompe disease from plasma	New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity	24 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Testing for clinical robustness, specificity and long-term stability of the biomarker	the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.	36 months

Collaborators and Investigators

• Sponsor: CENTOGENE GmbH Rostock

Publications and helpful links

Helpful Links

• Centogene is one of the leading laboratories focusing on genetic testing for rare hereditary disorders. We now offer more than 2200 routine genetic and biochemical tests.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 20, 2018
• Primary Completion (ACTUAL): December 31, 2021
• Study Completion (ACTUAL): December 31, 2021

Study Registration Dates

• First Submitted: October 21, 2011
• First Submitted That Met QC Criteria: October 21, 2011
• First Posted (ESTIMATE): October 24, 2011

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Biomarker; Pompe Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Stomatognathic Diseases; Mouth Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Sleep Apnea Syndromes; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Intracranial Arterial Diseases; Lysosomal Storage Diseases, Nervous System; Aneurysm; Glycogen Storage Disease; Hypertrophy; Tongue Diseases; Heart Diseases; Sleep Apnea, Obstructive; Lung Diseases; Muscle Weakness; Intracranial Aneurysm; Glycogen Storage Disease Type II; Splenomegaly; Macroglossia
• Other Study ID Numbers: BP 06-2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No