Studies of Inherited Diseases of Metabolism

Family Studies in Metabolic Diseases and Mineral Metabolism

Diseases of mineral metabolism such as familial multiple endocrine neoplasia type 1 (FMEN1), familial hypocaliuric hypercalcemia (FHH), familial hyperparathyroidism (FH), and pseudohypoparathyroidism (PHP) are known as hereditary abnormalities. Meaning these conditions are passed from parents to their children through genes. These specific conditions result in abnormal levels of calcium in the blood.

This study was designed to help researchers understand more about the genes that are responsible for these disorders. By learning more about the genetic process involved in hereditary abnormalities, new tests and treatments can be developed.

Subjects for this study will be members of families that have had relatives diagnosed with a disease of mineral metabolism. Participants will be asked to give blood samples for DNA extraction. DNA is the part of cells that carries genetic information.

The DNA will be analyzed and the results given to the subjects. Genetic counseling will be provided to subjects to aid in interpreting their results....

Study Overview

Status

Completed

Detailed Description

Familial multiple endocrine neoplasia type 1 (MEN1), familial hypocalciuric (or familial benign) hypercalcemia (FHH), hyperparathyroidism - jaw tumor syndrome (HPT-JT), other causes of familial isolated hyperparathyroidism (FIHP), and pseudohypoparathyroidism (PHP) are disorders of metabolism that are generally inherited in an autosomal dominant fashion. MEN1 is characterized by overgrowth and hyperfunction of the parathyroids, anterior pituitary and gastrointestinal endocrine tissue. MEN1, p15, p18, p21, and p27 are identified genes for MEN1- like states. FHH is characterized by a usually benign syndrome sometimes mistaken for typical primary hyperparathyroidism, which may result in unnecessary and unsuccessful parathyroid surgery. The CASR gene for the calcium-sensing receptor of the parathyroid cell is mutated in most FHH kindreds; a minority of kindreds with FHH have mutation of the GNA11 or AP2S1 gene. HPT-JT is a distinctive subtype of familial isolated hyperparathyroidism that has combinations of parathyroid adenoma, parathyroid cancer, jaw tumor, uterus tumor, kidney tumor and kidney cysts. It is caused by mutation of the CDC73/HRPT2 gene. PHP is characterized by parathyroid hormone resistance, and one form is associated with mutations in the gene encoding the alpha subunit of the stimulatory G protein. We are continuing to collect blood and tissue samples from affected and unaffected members of kindreds with known or suspected MEN1, FHH, HPT-JT, FIHP, PHP, and related disorders for the purpose of geneticanalysis and gene identification. In most cases, the procurement of specimens under this protocol will be at an off-site location. Samples will be processed for extraction of DNA and RNA.

Study Type

Observational

Enrollment (Actual)

969

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Subjects for this study will be members of families that have had relatives diagnosed with a disease of mineral metabolism. Participants will be asked to give blood samples for DNA extraction. DNA is the part of cells that carries genetic information. The DNA will be analyzed and the results given to the subjects. Genetic counseling will be provided to subjects to aid in interpreting their results.

Description

  • ELIGIBILITY CRITERIA:

    1. Patient has possible form of familial hyperparathyroidism. Or case is a clinically unaffected first degree relative of such a patient.
    2. The lower age limit to enter a clinically affected minor into the study is >= 4 years old. However, asymptomatic and possibly unaffected cases will not be enrolled, and blood will not be drawn, before age 5 years in MEN1, MEN1-like, HPT-JT, or FIHP kindreds or before age 10 in FHH kindreds.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
1
Members of families that have had relatives diagnosed with a disease of mineral metabolism. Participants will be asked to give blood samples for DNA extraction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of metabolic diseases
Time Frame: Yearly
Studies will be focused around forms of hereditary hypercalcemia, MEN1, FHH, HPT-JT, and FIHP as well as other disorders of mineral metabolism like PHP. In doing so, we will test the hypothesis that MEN1 and MEN1-like states develop as a result of a germ line mutation in MEN1 or a CDKI gene, define the mutations present in the affected members of MEN1 kindreds, and assess the frequency of such mutations in patients with apparently sporadic disease.
Yearly

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Smita Jha, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 19, 1993

Primary Completion (Actual)

January 13, 2023

Study Completion (Actual)

January 13, 2023

Study Registration Dates

First Submitted

November 3, 1999

First Submitted That Met QC Criteria

November 3, 1999

First Posted (Estimate)

November 4, 1999

Study Record Updates

Last Update Posted (Actual)

January 20, 2023

Last Update Submitted That Met QC Criteria

January 19, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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