Lysosomal Storage DisordersNCT00001215
Genetic Studies of Lysosomal Storage Disorders
An observational study of Lysosomal Storage Disorders and Gaucher Disease, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
The purpose of this study is to identify genetic, biochemical, and clinical factors that are associated with disease severity in people with Gaucher disease and other lysosomal storage disorders. Read more about this study
- Who is it for?
- Ages 1 week to 110 yearsHealthy volunteers can take part
- Conditions the study is for
- Lysosomal Storage Disorders, Gaucher Disease, Parkinson Disease
- How many people
- 1,000 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Mar 1995to not given
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 week to 110 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patient (or family members of patient) must be found to have or be a carrier of a documented lysosomal storage disorder.@@@
Who may be able to join
- For inclusion, the participant, of any age after birth, on initial screening must be found to have or be a carrier of a documented lysosomal storage disorder or be a family member of a documented proband. Healthy controls, > 18 years of age, will be recruited through the NIH healthy volunteer pool or we will invite unaffected spouses or relatives to participate. Healthy controls are necessary to determine the frequency of motor and non-motor symptoms in the general population. Parkinson disease patients, > 18 years of age, will be recruited from the Parkinson disease clinic at the NIH or by self-referral and will also be used for phenotypic comparison with GBA1-associated parkinsonism.
- Individuals who, in the opinion of the Investigator, are unable to comply with the protocol or have medical or social conditions that would potentially increase the risk of participation will be excluded from enrolling in the study. There will be no exclusion based upon age, gender, ethnicity, socioeconomic status, or any other factor. Cognitively impaired individuals may be enrolled if the legal guardian or durable power of attorney (DPA) consents, and assent will be obtained, when appropriate because a significant portion of patients with neurodegenerative disorders may develop cognitive impairment and it is important to include this information in the clinical phenotype. Pregnant or nursing women will also be included because all evaluations and procedures in this protocol do not pose risk to the mother and the fetus as no radiation or imaging studies will be performed for research purpose. Pregnancy in patients with GD and other lysosomal storage disorders presents specific challenges with regards to skeletal, hematological, and possibly visceral complications throughout gestation. It is important to capture the natural history of the disease during pregnancy to assess benefits of initiation/continuation/discontinuation of therapy depending on clinical signs and symptoms. Information obtained from participation of this population is of great value for counseling, prevention of complications, and prognostic implications. Participants are free to refuse any evaluation without affecting participation in this protocol.
- These are generally pan-ethnic disorders. Efforts will be made to include any patient from an under-represented minority with these disorders.
- Family members eligible/recruited include adult obligate carrier relatives, parents and siblings of Gaucher disease probands, and/or any relative with and without parkinsonism, where noncarriers volunteer for participation to serve as controls.
- Eligibility criteria for healthy and PD control group participants include healthy participants recruited from the Healthy volunteers office or healthy non-mutation carriers family members who voluntarily agree to participate. Patients with Parkinson disease who do not carry GBA1 mutations are eligible to participate to serve as controls
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Studies of Genetic Heterogeneity in Patients With Lysosomal Storage Disorders
The purpose of this study is to identify genetic, biochemical, and clinical factors that are associated with disease severity in people with Gaucher disease and other lysosomal storage disorders.
There is a vast spectrum of clinical manifestations in people with Gaucher disease as well as other lysosomal storage disorders. This study will evaluate patients with lysosomal disorders on an outpatient or inpatient basis in order to better characterize the clinical, genetic, and pathophysiological features of these disorders. Participants will be re-evaluated on an annual basis....
Read the detailed description
There is a vast spectrum of clinical manifestations encountered in individuals with lysosomal storage diseases. Lysosomal storage disorders occur when an enzyme necessary for breaking down intracellular fats, proteins, recycled products and organelles in the cell is deficient. As a result, substrate accumulates within the lysosomes affecting different organ systems. The most common lysosomal storage disease, Gaucher disease (GD), results from the inherited deficiency of the enzyme glucocerebrosidase, which breaks down the lipid glucocerebroside. The disease is characterized by extremely variable manifestations, with some patients presenting in childhood with hepatosplenomegaly, anemia, thrombocytopenia and bony problems, some in infancy with a lethal neurodegenerative course, while others remain asymptomatic into their eighth decade. GD has traditionally been divided into three clinical subtypes, type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (chronic neuronopathic) delineated by the absence or presence of neurologic involvement and its rate of progression. Some patients, however, defy classification into these three categories, and it may be more accurate to regard GD as a continuum of phenotypes. In addition, patients and carriers of mutations in GBA1, the gene for GD, are at increased risk for developing Parkinson disease (PD) and related neurodegenerative disorders.
This is a longitudinal natural history study of patients with lysosomal storage disorders with emphasis on phenotypic heterogeneity of GD and those at risk for the development of parkinsonism. Our goal is to identify genetic, biochemical, and clinical parameters that are associated with disease severity in individuals with lysosomal storage disorders to identify individuals with milder or early phenotypic manifestations, and to explore the natural history and extent of associated clinical manifestations. We also study subjects with GBA1 mutations who are at higher risk for developing parkinsonism to identify early disease manifestations and potential biomarkers. Participants are evaluated at the NIH to better characterize the clinical, genetic and pathophysiological features of these disorders. In order to better understand the entire effect of the enzyme deficiencies and the function of the specific proteins involved, emphasis is placed on individuals with atypical presentations. In particular, we will focus on subjects with GD and PD, to better understand the association between the two disorders. Following an initial comprehensive workup, participants will be studied either in the inpatient wards or the outpatient clinic and will be re-evaluated at periodic intervals longitudinally.
- Keywords
- Variants, Chemical Phenotype, Enzyme, Phenotype, Glucocerebrosidase, Natural History
- Medical subject headings
- Lysosomal Storage Diseases, Gaucher Disease, Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Control | healthy volunteers | |
| Family Member | a family member of a documented proband | |
| Patient | the participant on initial screening must be found to have or be a carrier of a documented lysosomal storage disorder |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Phenotypes
The purpose of this study is to clearly describe the clinical phenotypes of individuals with lysosomal storage diseases in order to better understand the pathophysiology of these disorders and to develop new therapies.
Measured: ongoing
Secondary outcomes (1)
development of Parkinsonism
We aim to identify factors that may be predictive of the development of Parkinsonism in an at-risk population
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start8 Mar 1995
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Lysosomal Storage DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ellen Sidransky, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001215
- Sponsor's protocol ID
- 860096
- Other IDs
- 86-HG-0096
- Status last verified
- 16 Sep 2026
- First submitted
- 3 Nov 1999
- Last updated
- 26 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: pending
Publications
Steward AM, Wiggs E, Lindstrom T, Ukwuani S, Ryan E, Tayebi N, Roshan Lal T, Lopez G, Schiffmann R, Sidransky E. Variation in cognitive function over time in Gaucher disease type 3. Neurology. 2019 Dec 10;93(24):e2272-e2283. doi: 10.1212/WNL.0000000000008618. Epub 2019 Nov 12.
PubMed 31719137Gary SE, Ryan E, Steward AM, Sidransky E. Recent advances in the diagnosis and management of Gaucher disease. Expert Rev Endocrinol Metab. 2018 Mar;13(2):107-118. doi: 10.1080/17446651.2018.1445524. Epub 2018 Mar 12.
PubMed 30058864Lopez G, Steward A, Ryan E, Groden C, Wiggs E, Segala L, Monestime GM, Tayebi N, Sidransky E. Clinical evaluation of sibling pairs with gaucher disease discordant for parkinsonism. Mov Disord. 2020 Feb;35(2):359-365. doi: 10.1002/mds.27916. Epub 2019 Nov 30.
PubMed 31785030
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studies of Genetic Heterogeneity in Patients With Lysosomal Storage Disorders
- ClinicalTrials.gov ID
- NCT00001215
- Acronym / sponsor ID
- 860096
- Keywords
- Variants, Chemical Phenotype, Enzyme, Phenotype, Glucocerebrosidase, Natural History
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 8 Mar 1995 (actual)
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to identify genetic, biochemical, and clinical factors that are associated with disease severity in people with Gaucher disease and other lysosomal storage disorders.
There is a vast spectrum of clinical manifestations in people with Gaucher disease as well as other lysosomal storage disorders. This study will evaluate patients with lysosomal disorders on an outpatient or inpatient basis in order to better characterize the clinical, genetic, and pathophysiological features of these disorders. Participants will be re-evaluated on an annual basis....
Detailed description
There is a vast spectrum of clinical manifestations encountered in individuals with lysosomal storage diseases. Lysosomal storage disorders occur when an enzyme necessary for breaking down intracellular fats, proteins, recycled products and organelles in the cell is deficient. As a result, substrate accumulates within the lysosomes affecting different organ systems. The most common lysosomal storage disease, Gaucher disease (GD), results from the inherited deficiency of the enzyme glucocerebrosidase, which breaks down the lipid glucocerebroside. The disease is characterized by extremely variable manifestations, with some patients presenting in childhood with hepatosplenomegaly, anemia, thrombocytopenia and bony problems, some in infancy with a lethal neurodegenerative course, while others remain asymptomatic into their eighth decade. GD has traditionally been divided into three clinical subtypes, type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (chronic neuronopathic) delineated by the absence or presence of neurologic involvement and its rate of progression. Some patients, however, defy classification into these three categories, and it may be more accurate to regard GD as a continuum of phenotypes. In addition, patients and carriers of mutations in GBA1, the gene for GD, are at increased risk for developing Parkinson disease (PD) and related neurodegenerative disorders.
This is a longitudinal natural history study of patients with lysosomal storage disorders with emphasis on phenotypic heterogeneity of GD and those at risk for the development of parkinsonism. Our goal is to identify genetic, biochemical, and clinical parameters that are associated with disease severity in individuals with lysosomal storage disorders to identify individuals with milder or early phenotypic manifestations, and to explore the natural history and extent of associated clinical manifestations. We also study subjects with GBA1 mutations who are at higher risk for developing parkinsonism to identify early disease manifestations and potential biomarkers. Participants are evaluated at the NIH to better characterize the clinical, genetic and pathophysiological features of these disorders. In order to better understand the entire effect of the enzyme deficiencies and the function of the specific proteins involved, emphasis is placed on individuals with atypical presentations. In particular, we will focus on subjects with GD and PD, to better understand the association between the two disorders. Following an initial comprehensive workup, participants will be studied either in the inpatient wards or the outpatient clinic and will be re-evaluated at periodic intervals longitudinally.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control | – | –healthy volunteers |
| Family Member | – | –a family member of a documented proband |
| Patient | – | –the participant on initial screening must be found to have or be a carrier of a documented lysosomal storage disorder |
Who may qualify
- Ages
- 1 week to 110 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patient (or family members of patient) must be found to have or be a carrier of a documented lysosomal storage disorder.@@@
Key inclusion criteria (5 listed)
- For inclusion, the participant, of any age after birth, on initial screening must be found to have or be a carrier of a documented lysosomal storage disorder or be a family member of a documented proband. Healthy controls, > 18 years of age, will be recruited through the NIH healthy volunteer pool or we will invite unaffected spouses or relatives to participate. Healthy controls are necessary to determine the frequency of motor and non-motor symptoms in the general population. Parkinson disease patients, > 18 years of age, will be recruited from the Parkinson disease clinic at the NIH or by self-referral and will also be used for phenotypic comparison with GBA1-associated parkinsonism.
- Individuals who, in the opinion of the Investigator, are unable to comply with the protocol or have medical or social conditions that would potentially increase the risk of participation will be excluded from enrolling in the study. There will be no exclusion based upon age, gender, ethnicity, socioeconomic status, or any other factor. Cognitively impaired individuals may be enrolled if the legal guardian or durable power of attorney (DPA) consents, and assent will be obtained, when appropriate because a significant portion of patients with neurodegenerative disorders may develop cognitive impairment and it is important to include this information in the clinical phenotype. Pregnant or nursing women will also be included because all evaluations and procedures in this protocol do not pose risk to the mother and the fetus as no radiation or imaging studies will be performed for research purpose. Pregnancy in patients with GD and other lysosomal storage disorders presents specific challenges with regards to skeletal, hematological, and possibly visceral complications throughout gestation. It is important to capture the natural history of the disease during pregnancy to assess benefits of initiation/continuation/discontinuation of therapy depending on clinical signs and symptoms. Information obtained from participation of this population is of great value for counseling, prevention of complications, and prognostic implications. Participants are free to refuse any evaluation without affecting participation in this protocol.
- These are generally pan-ethnic disorders. Efforts will be made to include any patient from an under-represented minority with these disorders.
- Family members eligible/recruited include adult obligate carrier relatives, parents and siblings of Gaucher disease probands, and/or any relative with and without parkinsonism, where noncarriers volunteer for participation to serve as controls.
- Eligibility criteria for healthy and PD control group participants include healthy participants recruited from the Healthy volunteers office or healthy non-mutation carriers family members who voluntarily agree to participate. Patients with Parkinson disease who do not carry GBA1 mutations are eligible to participate to serve as controls
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Clinical Phenotypes
Time frame: ongoing
The purpose of this study is to clearly describe the clinical phenotypes of individuals with lysosomal storage diseases in order to better understand the pathophysiology of these disorders and to develop new therapies.
1 secondary outcome
development of Parkinsonism
Time frame: ongoing
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Background: PubMed 31719137Steward AM, Wiggs E, Lindstrom T, Ukwuani S, Ryan E, Tayebi N, Roshan Lal T, Lopez G, Schiffmann R, Sidransky E. Variation in cognitive function over time in Gaucher disease type 3. Neurology. 2019 Dec 10;93(24):e2272-e2283. doi: 10.1212/WNL.0000000000008618. Epub 2019 Nov 12.
- Background: PubMed 30058864Gary SE, Ryan E, Steward AM, Sidransky E. Recent advances in the diagnosis and management of Gaucher disease. Expert Rev Endocrinol Metab. 2018 Mar;13(2):107-118. doi: 10.1080/17446651.2018.1445524. Epub 2018 Mar 12.
- Background: PubMed 31785030Lopez G, Steward A, Ryan E, Groden C, Wiggs E, Segala L, Monestime GM, Tayebi N, Sidransky E. Clinical evaluation of sibling pairs with gaucher disease discordant for parkinsonism. Mov Disord. 2020 Feb;35(2):359-365. doi: 10.1002/mds.27916. Epub 2019 Nov 30.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. pending
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ellen Sidransky, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lysosomal Storage Disorders and Gaucher Disease, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Phenotypes (time frame: ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001215, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.