What are the other Names for this Condition? (Also known as/Synonyms)

• Familial Isolated Primary Hyperparathyroidism
• Familial Primary Hyperparathyroidism
• Hyperparathyroidism 1

What is Familial Isolated Hyperparathyroidism? (Definition/Background Information)

• Familial Isolated Hyperparathyroidism (FIHP) is an inherited form of primary hyperparathyroidism that is not associated with other features. The age of diagnosis varies from childhood to adulthood
• In FIHP, tumors involving the parathyroid glands cause the production and release of excess parathyroid hormone, which in turn causes increased calcium in the blood (hypercalcemia). The tumors are usually benign, but a cancerous tumor can develop in rare cases
• Abnormal levels of calcium cause many of the symptoms of FIHP, including kidney stones, nausea, vomiting, high blood pressure (hypertension), weakness, and fatigue. Osteoporosis often also develops
• Familial Isolated Hyperparathyroidism may be caused by mutations in the MEN1, CDC73 (also known as the HRPT2 gene), or CASR genes and is typically inherited in an autosomal dominant manner. In some cases, the cause is unknown
• Treatment for Familial Isolated Hyperparathyroidism often includes surgical removal of the affected gland(s)

(Source: Familial Isolated Hyperparathyroidism; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Familial Isolated Hyperparathyroidism? (Age and Sex Distribution)

• Familial Isolated Hyperparathyroidism is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Familial Isolated Hyperparathyroidism? (Predisposing Factors)

• A positive family history may be an important risk factor, since Familial Isolated Hyperparathyroidism can be inherited
• Currently, no other risk factors have been clearly identified for FIHP

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Familial Isolated Hyperparathyroidism? (Etiology)

• Familial Isolated Hyperparathyroidism may be caused by mutations in the MEN1, CDC73 (also known as the HRPT2 gene), or CASR genes
• Presently, no gene has been associated exclusively with FIHP. FIHP is typically inherited in an autosomal dominant manner
• In some cases, the cause is unknown

(Source: Familial Isolated Hyperparathyroidism; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Familial Isolated Hyperparathyroidism?

The signs and symptoms of Familial Isolated Hyperparathyroidism may include:

• Hypercalcemia
• Primary hyperparathyroidism

(Source: Familial Isolated Hyperparathyroidism; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Familial Isolated Hyperparathyroidism Diagnosed?

• The diagnosis of Familial Isolated Hyperparathyroidism is primarily a diagnosis of exclusion. This means that it is diagnosed when no symptoms or genetic features of other forms of familial hyperparathyroidism are present
• FIHP may be the only feature of another condition that is not manifesting completely, or it may be a distinct condition due to mutations in genes that have not yet been identified. Clinical exams, laboratory tests, and histological (microscopic) findings are needed before making a diagnosis of FIHP
• A diagnosis of Familial Isolated Hyperparathyroidism may include the findings of:
  • Hypercalcemia (defined as a serum calcium level greater than 10.5 mg/dL)
  • Inappropriately high parathyroid hormone (PTH) concentrations
  • Parathyroid adenomas
  • Exclusion of multiple endocrine neoplasia type 1 (MEN 1) and hyperparathyroidism-jaw tumor syndrome (HPT-JT)

(Source: Familial Isolated Hyperparathyroidism; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Familial Isolated Hyperparathyroidism?

The complications of Familial Isolated Hyperparathyroidism may include:

• Kidney stones
• Chronic kidney malfunction leading to kidney failure
• Abnormal heart function including arrhythmia
• Memory problems

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Familial Isolated Hyperparathyroidism Treated?

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of Familial Isolated Hyperparathyroidism:

• Cinacalcet
• FDA-approved indication: Treatment of hypercalcemia in adult patients with primary hyperparathyroidism for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy

(Source: Familial Isolated Hyperparathyroidism; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Familial Isolated Hyperparathyroidism be Prevented?

Currently, Familial Isolated Hyperparathyroidism may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Familial Isolated Hyperparathyroidism? (Outcomes/Resolutions)

• The prognosis of Familial Isolated Hyperparathyroidism is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Familial Isolated Hyperparathyroidism:

• Mutations in the MEN1 and CDC73 genes cause other conditions in which hyperparathyroidism is one of many features, but some people with mutations in these genes have only isolated hyperparathyroidism 
• Familial Isolated Hyperparathyroidism can also represent an early stage of other syndromes

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/