Clinical trial NCT03812042: Screening of Lysosomal Storage Disorders Diseases in Minority Groups
Official title: Enzymatic and Genotypic Screening of Lysosomal Storage Diseases in Minority Groups
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lysosomal Storage Diseases
Keywords: Gaucher disease
Fabry disease
Pompe disease
Gangliosidoses
Lead sponsor: Lysosomal and Rare Disorders Research and Treatment Center, Inc.
Sponsor class: OTHER
First posted: 2019-01-22
Enrollment: 100000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: ECOLOGIC_OR_COMMUNITY
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility 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

Primary outcomes:
measure: Enzyme activity analysis to identify subjects with Lysosomal storage disorders
timeFrame: 5 years
measure: Genotypic analysis of subjects with abnormal enzyme activity
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Fairfax
country: United States
facility: LDRTC
state: Virginia
Study officials:
affiliation: LDRTC
name: Renuka Limgala, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: LDRTC
name: Margarita M Ivanova, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: LDRTC
name: Ozlem Goker-Alpan, MD
role: PRINCIPAL_INVESTIGATOR
References: