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Screening of Lysosomal Storage Disorders Diseases in Minority Groups

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ClinicalTrials.gov Identifier: NCT03812042
Recruitment Status : Active, not recruiting
First Posted : January 21, 2019
Last Update Posted : January 21, 2019
Sponsor:
Information provided by (Responsible Party):
Lysosomal and Rare Disorders Research and Treatment Center, Inc.

Brief Summary:
Aim is to undertake a screening study that identifies undiagnosed patients with LSDs and determine the prevalence of these diseases with special focus on underrepresented minority groups.

Condition or disease Intervention/treatment
Lysosomal Storage Diseases Diagnostic Test: Enzyme assay and molecular sequencing

Detailed Description:

Lysosomes are small, cytoplasmic organelles that contain several acid hydrolase enzymes. These enzymes break down foreign materials and cellular debris allowing the lysosomes to act as recycling centers for the cells. Following DNA transcription, lysosomal enzymes are produced in the endoplasmic reticulum and targeted to lysosomes by specific recognition markers. If one of the enzymes is absent or if its function is diminished due to either an altered amino acid sequence of the protein or defective intracellular trafficking, the macromolecules metabolized by the specific enzyme will gradually accumulate in the lysosomes. Abnormal substrate storage leads to cellular dysfunction followed by cell death ultimately manifesting as tissue damage and organ failure.

More than 50 metabolic disorders resulting from defective lysosomal enzyme function have been described and are classified as lysosomal storage disorders (LSDs). Although individually uncommon (less than 1 in 100,000), the combined incidence of this group of genetic disorders is about 1 in 5,000 to 1 in 10,000. The prevalence might be even higher than predicted due to undiagnosed instances or misdiagnosis of milder cases.

Most of LSDs are inherited in an autosomal recessive manner except two disorders: Fabry disease and Hunter syndrome, which are X chromosome linked. Two healthy carriers of the same autosomal recessive disease may have an affected child. Usually the carriers are unaware of their carrier status prior to screening or until they have a sick child. These disorders are more common in communities with high consanguinity and where cousin marriages are allowed. In the case of X-linked diseases, the mutant gene is passed down from one generation to the next one in a specific way. If a male has an abnormal copy of the specific gene, he will show the typical presentation of the disease. If a woman has an abnormal copy of the specific gene, she may develop some milder symptoms of the disease due to random X- inactivation.

Screening for LSDs is performed by measuring enzymatic activity in peripheral blood. The most cost effective and convenient way is to use dried filter paper blood spots. A positive screening result has to be followed by a confirmatory enzymatic testing using white blood cells, plasma or cultured skin fibroblasts and/or DNA mutation analysis. The importance of screening for LSDs has been recognized by several state governments as these tests are being included in many newborn screening programs. Although newborn screening helps to identify patients early on, there is still an unmet need for population screening and for identifying patients with reversible tissue damage. LSDs cause serious and progressive problems with multiple body systems. Therapy is available and is promising in most cases. Importantly, patients with LSDs require thorough management plans for their complex health issues.


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Study Type : Observational
Estimated Enrollment : 100000 participants
Observational Model: Ecologic or Community
Time Perspective: Prospective
Official Title: Enzymatic and Genotypic Screening of Lysosomal Storage Diseases in Minority Groups
Actual Study Start Date : March 17, 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


Group/Cohort Intervention/treatment
Screen population
The study population will comprise of patients of healthcare institutions in the Washington, D.C. metro area including but not limited to hospitals, clinics, and doctor's offices.
Diagnostic Test: Enzyme assay and molecular sequencing
Enzyme assay and molecular sequencing on relevant samples conducted from left over blood samples




Primary Outcome Measures :
  1. Enzyme activity analysis to identify subjects with Lysosomal storage disorders [ Time Frame: 5 years ]
    To identify patients with LSDs using enzymatic activity specific to individual lysosomal storage disorders using left-over blood of blood samples collected as part of standard clinical care.

  2. Genotypic analysis of subjects with abnormal enzyme activity [ Time Frame: 5 years ]
    Samples from subjects with abnormally low enzyme activity will be used for targeted sequencing analysis to diagnose any pathologic mutations.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The study population will comprise of patients of healthcare institutions in the Washington, D.C. and Richmond, Virginia areas including but not limited to hospitals, clinics, and doctor's offices.
Criteria

Inclusion Criteria:

  • To be enrolled in this study the subject must meet the following (inclusion) criteria:

    • Subject is greater than or equal to 1 day of age and less than or equal to 100 years of age
    • Subject is managed by a physician in the Washington, D.C and Richmond, VA metro area
    • Subject is getting blood work as part of standard clinical care and there is at least 60 uL blood remained in a tube after all clinical tests were run

Exclusion Criteria:

  • subjects must not meet any of the following (exclusion) criteria:

    • Absolute contraindication for blood drawing
    • Subject cannot be traced back by the referring physician upon a positive screening result

Information from the National Library of Medicine

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): NCT03812042


Locations
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United States, Virginia
LDRTC
Fairfax, Virginia, United States, 22030
Sponsors and Collaborators
Lysosomal and Rare Disorders Research and Treatment Center, Inc.
Investigators
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Principal Investigator: Renuka Limgala, PhD LDRTC
Principal Investigator: Margarita M Ivanova, PhD LDRTC
Principal Investigator: Ozlem Goker-Alpan, MD LDRTC

Additional Information:
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Responsible Party: Lysosomal and Rare Disorders Research and Treatment Center, Inc.
ClinicalTrials.gov Identifier: NCT03812042     History of Changes
Other Study ID Numbers: 16-LDRTC-04
First Posted: January 21, 2019    Key Record Dates
Last Update Posted: January 21, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lysosomal and Rare Disorders Research and Treatment Center, Inc.:
Gaucher disease
Fabry disease
Pompe disease
Gangliosidoses
Additional relevant MeSH terms:
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Lysosomal Storage Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn