Diagnosis and Treatment of Patients With Inborn Errors of Metabolism

NCT ID: NCT00369421

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

4000 participants

Study Classification

OBSERVATIONAL

Study Start Date

1978-09-12

Brief Summary

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Researchers intend on diagnosing and treating certain inborn errors of metabolism. By doing this researchers hope to expand their knowledge about these disorders and provide access to patients of interest for research, teaching, and clinical experience.

Patients participating in this study will be examined and treated on an out patient basis, if practical. However, patients requiring specialized tests or treatments will be admitted to the NIH Clinical Center as necessary. Researchers will use only accepted medical procedures in diagnosing (medical history, physical examinations, X-ray studies, eye examinations, blood tests, and urine tests) and treating the patients involved in this study. Additional tests may be required on a case to case basis.

Many patients seen in this study will go on to be enrolled in a specific disease-related research study.\<TAB\>

Detailed Description

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Study Description:

We propose to characterize the etiology and natural history of rare inborn errors of metabolism and other genetic disorders, both known and yet-to-be discovered. In so doing, we will expand our knowledge about these disorders and provide access to patients of interest for research, teaching, and clinical experience.

Objectives:

The overall aim of this protocol is to advance our knowledge of genetic disorders.

Conditions

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Arterial Calcification Due to Deficiency of CD73

Keywords

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Biochemical Diseases Rare Diseases Family Studies Screening Next Generation Sequencing Natural History

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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Healthy Volunteers

Healthy Volunteers

No interventions assigned to this group

Patients

Patients with unique disorders

No interventions assigned to this group

Unaffected family members

Unaffected family members of patients

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

Participants 1 month or older will have been or will be referred to this protocol with a known or suspected inborn error of metabolism, heritable disorder, or genetic predisposition. Participants over two years of age will be admitted only if they are medically stable and require admission to the Clinical Center for diagnosis. Children ages 1 month to 2 years or under 12 kg will be reviewed by the Pediatric Consult Service prior to scheduling and if approved will be evaluated.

Examples of disorders that will be under this protocol include inherited developmental defects or diatheses toward infections, cancer, or an environmentally induced disease. The principal investigator, along with consulting specialists, will review the medical records of prospective participants and offer admission based upon the potential to help the individual, to learn from the participant, or to initiate clinical or basic research suggested by the participant s workup. This protocol is not intended to serve as an umbrella protocol for small studies of specific disorders. In general, no more than 5 families known to have the same disorder will be investigated under this protocol.

Some participants will be relatives of patients with known diagnoses, and their specimens will be obtained for the purpose of heterozygote testing or to serve as controls to help diagnose the proband. All participants shall be seen as inpatients, outpatients or via Telehealth at the discretion of the principal investigator, based upon particular research interests and expertise. Normal adult volunteers aged 18 years or older will be enrolled to provide control blood and urine specimens.

Exclusion Criteria

* Participants under 1 month of age will not be seen at the NIH Clinical center because care is more readily proffered to older individuals at the Clinical Center.
* Participants over two years of age will not be admitted if they are medically unstable and do not require admission to the Clinical Center for diagnosis.
* Pregnant women are excluded.
Minimum Eligible Age

1 Month

Maximum Eligible Age

115 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Human Genome Research Institute (NHGRI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William A Gahl, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Human Genome Research Institute (NHGRI)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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William A Gahl, M.D.

Role: CONTACT

Phone: (301) 402-2739

Email: [email protected]

Facility Contacts

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For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Role: primary

References

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Gahl WA, Adamson M, Kaiser-Kupfer I, Ludwig IH, O'Connell HJ, Cohen W, Barranger J. Biochemical phenotyping of a single sibship with both cystinosis and Fabry disease. J Inherit Metab Dis. 1985;8(3):127-31. doi: 10.1007/BF01819297.

Reference Type BACKGROUND
PMID: 3027448 (View on PubMed)

Bernardini I, Rizzo WB, Dalakas M, Bernar J, Gahl WA. Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome. J Clin Invest. 1985 Apr;75(4):1124-30. doi: 10.1172/JCI111806.

Reference Type BACKGROUND
PMID: 3988933 (View on PubMed)

Kaiser-Kupfer MI, Caruso RC, Minkler DS, Gahl WA. Long-term ocular manifestations in nephropathic cystinosis. Arch Ophthalmol. 1986 May;104(5):706-11. doi: 10.1001/archopht.1986.01050170096030.

Reference Type BACKGROUND
PMID: 3518682 (View on PubMed)

Theng EH, Brewer CC, Oheim R, Zalewski CK, King KA, Delsmann MM, Rolvien T, Gafni RI, Braddock DT, Jeffrey Kim H, Ferreira CR. Characterization of hearing-impairment in Generalized Arterial Calcification of Infancy (GACI). Orphanet J Rare Dis. 2022 Jul 19;17(1):273. doi: 10.1186/s13023-022-02410-w.

Reference Type DERIVED
PMID: 35854274 (View on PubMed)

Cohen JI, Manoli I, Dowdell K, Krogmann TA, Tamura D, Radecki P, Bu W, Turk SP, Liepshutz K, Hornung RL, Fassihi H, Sarkany RP, Bonnycastle LL, Chines PS, Swift AJ, Myers TG, Levoska MA, DiGiovanna JJ, Collins FS, Kraemer KH, Pittaluga S, Jaffe ES. Hydroa vacciniforme-like lymphoproliferative disorder: an EBV disease with a low risk of systemic illness in whites. Blood. 2019 Jun 27;133(26):2753-2764. doi: 10.1182/blood.2018893750. Epub 2019 May 7.

Reference Type DERIVED
PMID: 31064750 (View on PubMed)

Thumbigere-Math V, Alqadi A, Chalmers NI, Chavez MB, Chu EY, Collins MT, Ferreira CR, FitzGerald K, Gafni RI, Gahl WA, Hsu KS, Ramnitz MS, Somerman MJ, Ziegler SG, Foster BL. Hypercementosis Associated with ENPP1 Mutations and GACI. J Dent Res. 2018 Apr;97(4):432-441. doi: 10.1177/0022034517744773. Epub 2017 Dec 15.

Reference Type DERIVED
PMID: 29244957 (View on PubMed)

Gunay-Aygun M, Zivony-Elboum Y, Gumruk F, Geiger D, Cetin M, Khayat M, Kleta R, Kfir N, Anikster Y, Chezar J, Arcos-Burgos M, Shalata A, Stanescu H, Manaster J, Arat M, Edwards H, Freiberg AS, Hart PS, Riney LC, Patzel K, Tanpaiboon P, Markello T, Huizing M, Maric I, Horne M, Kehrel BE, Jurk K, Hansen NF, Cherukuri PF, Jones M, Cruz P, Mullikin JC, Nurden A, White JG, Gahl WA, Falik-Zaccai T. Gray platelet syndrome: natural history of a large patient cohort and locus assignment to chromosome 3p. Blood. 2010 Dec 2;116(23):4990-5001. doi: 10.1182/blood-2010-05-286534. Epub 2010 Aug 13.

Reference Type DERIVED
PMID: 20709904 (View on PubMed)

Maynard DM, Heijnen HF, Gahl WA, Gunay-Aygun M. The alpha-granule proteome: novel proteins in normal and ghost granules in gray platelet syndrome. J Thromb Haemost. 2010 Aug;8(8):1786-96. doi: 10.1111/j.1538-7836.2010.03932.x. Epub 2010 May 27.

Reference Type DERIVED
PMID: 20524979 (View on PubMed)

Huizing M, Dorward H, Ly L, Klootwijk E, Kleta R, Skovby F, Pei W, Feldman B, Gahl WA, Anikster Y. OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria. Mol Genet Metab. 2010 Jun;100(2):149-54. doi: 10.1016/j.ymgme.2010.03.005. Epub 2010 Mar 16.

Reference Type DERIVED
PMID: 20350831 (View on PubMed)

Related Links

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Other Identifiers

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76-HG-0238

Identifier Type: -

Identifier Source: secondary_id

760238

Identifier Type: -

Identifier Source: org_study_id