Familial hypocalciuric hypercalcemia

A genetic condition characterized by elevated blood calcium levels and low urinary calcium excretion

Familial hypocalciuric hypercalcemia
Synonyms	FHH
Pronounce	N/A
Specialty	N/A
Symptoms	Mild hypercalcemia, low urinary calcium excretion
Complications	Rarely pancreatitis
Onset	Congenital
Duration	Lifelong
Types	N/A
Causes	Mutations in the calcium-sensing receptor gene
Risks	N/A
Diagnosis	Blood tests, genetic testing
Differential diagnosis	Primary hyperparathyroidism, Hypercalcemia of malignancy
Prevention	N/A
Treatment	Usually none required
Medication	N/A
Prognosis	Generally benign
Frequency	Rare
Deaths	N/A

Familial hypocalciuric hypercalcemia (FHH) is a rare genetic disorder characterized by elevated levels of calcium in the blood (hypercalcemia) and low levels of calcium in the urine (hypocalciuria). It is typically a benign condition that is inherited in an autosomal dominant pattern.

Pathophysiology

FHH is primarily caused by mutations in the calcium-sensing receptor (CaSR) gene, which is located on chromosome 3q21.1. The CaSR is a G-protein coupled receptor that plays a crucial role in maintaining calcium homeostasis by regulating parathyroid hormone (PTH) secretion and renal calcium excretion. Mutations in the CaSR gene lead to a reduced sensitivity to extracellular calcium levels, resulting in inappropriate secretion of PTH and increased renal reabsorption of calcium.

Clinical Presentation

Most individuals with FHH are asymptomatic and the condition is often discovered incidentally during routine blood tests showing mild hypercalcemia. In rare cases, patients may experience symptoms such as fatigue, weakness, or mild neuropsychiatric disturbances. Unlike primary hyperparathyroidism, FHH does not typically lead to significant complications such as kidney stones or bone disease.

Diagnosis

The diagnosis of FHH is based on the presence of hypercalcemia, low urinary calcium excretion, and a family history of the condition. Genetic testing can confirm the diagnosis by identifying mutations in the CaSR gene. It is important to differentiate FHH from primary hyperparathyroidism, as the management of these conditions differs significantly.

Management

FHH is generally considered a benign condition that does not require treatment. Patients are usually monitored with periodic blood tests to ensure that calcium levels remain stable. In rare cases where symptoms are present, supportive care may be provided.

Genetic Counseling

Since FHH is inherited in an autosomal dominant manner, genetic counseling is recommended for affected families. Each child of an affected individual has a 50% chance of inheriting the condition.

Also see

• Hypercalcemia
• Primary hyperparathyroidism
• Calcium-sensing receptor
• Genetic disorders