Studies of Inherited Diseases of Metabolism

Study Description

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Brief 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.

Condition or disease
Hypercalcemia; Hyperparathyroidism; Multiple Endocrine Neoplasia

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 (FIH), 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 MEN 1- 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 of most FHH kindreds;a minority of kindreds with FHH have mutation of the GA11 or AP2S 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 HRPT2 gene. PHP is characterized by parathyroid hormone resistance, and one form is associated with mutations in the gene encoding 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, FIH, PHP, and related disorders for the purpose of genetic analysis and gene identification. In most cases, the procurement of specimens will be at an off-site location. Samples will be processed for extraction of DNA and RNA.

Study Design

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Study Type :	Observational
Estimated Enrollment :	2000 participants
Official Title:	Family Studies in Metabolic Diseases and Mineral Metabolism
Study Start Date :	April 21, 1993

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

• INCLUSION CRITERIA

Patients with known or suspected metabolic disorders of such as MEN 1, MEN 1-like states, FHH, HPT-JT, FIH, FIC, PHP and their first degree relatives (parents, siblings and offspring) and spouses. For the most part only one index case in a family will be tested.

Pre-test counseling by an NIDDK investigator.

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Craig S Cochran, R.N.	(301) 402-1880	craigc@bdg10.niddk.nih.gov
Contact: William F Simonds, M.D.	(301) 496-9299	wfs@helix.nih.gov

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Principal Investigator:	William F Simonds, M.D.	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

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. Review.

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.

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.

Responsible Party:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00001345 History of Changes
Other Study ID Numbers:	930127; 93-DK-0127
First Posted:	November 4, 1999
Last Update Posted:	March 29, 2018
Last Verified:	January 5, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ):

Hypercalcemia; Multiple Endocrine Neoplasia (MEN); Familial Hypocalciuric Hypercalcemia; Hyperparathyroidism; Linkage Analysis

Additional relevant MeSH terms:

Neoplasms; Hyperparathyroidism; Hypercalcemia; Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Parathyroid Diseases; Endocrine System Diseases	Calcium Metabolism Disorders; Metabolic Diseases; Water-Electrolyte Imbalance; Neoplasms by Site; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn