Studies of Inherited Diseases of Metabolism

Official Title: “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.

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, familial carcinoid tumor, 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. The gene for MEN1 on chromosome 11q13 was cloned in 1997. P15, p18, p 21 are other genes for MEN1-like states.

Familial carcinoid tumor can be a component of MEN1 or isolated without other endocrine tumors (FIC). 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 was cloned, and members of most FHH kindreds have been noted to have mutations in this gene.

HPT-JT is a distinctive subtype of familial isolated hyperparathyroidism (FIH) that has combinations of parathyroid adenoma, parathyroid cancer, jaw 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 located on chromosome 20q13. We are continuing to collect blood samples and tissue samples from affected and unaffected members of known and suspected MEN1, FIC, FHH, HPT-JT, FIH, PHP, and related kindreds 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/or the creation of transformed cell lines. This will provide a ready source of DNA and other molecules for genetic analysis to delineate the genetic and molecular basis of these disorders. As genetic analyses often reveal conclusive information about these disorders, genetic counseling is being offered to the individual family members who have provided the specimens.

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) NIH

Overall Clinical Trial Officials and Contacts

Overall Contact: Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00001345

Study ID Number: 930127

ClinicalTrials.gov Identifier: NCT00001345

Health Authority: United States: Federal Government

NIH Clinical Center Detailed Web Page