Studies of Inherited Diseases of Metabolism

Multiple Endocrine Neoplasia Clinical Trial

Official title:

Family Studies in Metabolic Diseases and Mineral Metabolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001345
• Other study ID #: 930127
• Secondary ID: 93-DK-0127
• Status: Completed
• Start date: August 19, 1993
• Est. completion date: January 13, 2023

Study information

• Verified date: January 2023
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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....

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 969
• Est. completion date: January 13, 2023
• Est. primary completion date: January 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

• 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.

Related Conditions & MeSH terms

• Endocrine Gland Neoplasms
• Multiple Endocrine Neoplasia
• Neoplasms

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, Debelenko LV, Zhuang Z, Lubensky IA, Liotta LA, Crabtree JS, Wang Y, Roe BA, Weisemann J, Boguski MS, Agarwal SK, Kester MB, Kim YS, Heppner C, Dong Q, Spiegel AM, Burns AL, Marx SJ. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science. 1997 Apr 18;276(5311):404-7. doi: 10.1126/science.276.5311.404. — View Citation

Marx SJ, Attie MF, Levine MA, Spiegel AM, Downs RW Jr, Lasker RD. The hypocalciuric or benign variant of familial hypercalcemia: clinical and biochemical features in fifteen kindreds. Medicine (Baltimore). 1981 Nov;60(6):397-412. doi: 10.1097/00005792-198111000-00002. No abstract available. — View Citation

Spiegel AM, Shenker A, Weinstein LS. Receptor-effector coupling by G proteins: implications for normal and abnormal signal transduction. Endocr Rev. 1992 Aug;13(3):536-65. doi: 10.1210/edrv-13-3-536. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of metabolic diseases	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

External Links

•   NIH Clinical Center Detailed Web Page