Studies of Inherited Diseases of Metabolism

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.

- ELIGIBILITY 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.

Patient has possible form of familial hyperparathyroidism. Or case is a clinically
unaffected first degree relative of such a patient.

There is no lower age limit to enter a clinically affected minor into the study. However,
asymptomatic and possibly unaffected cases will not be enrolled.

A pregnant woman could be included in aspects of the research study that present no greater
than minimal risk to patient or fetus, such as DNA testing of maternal blood.