Familial hypocalciuric hypercalcemia (FHCH) is a genetic disorder characterized by elevated blood calcium levels (hypercalcemia) and low urinary calcium excretion (hypocalciuria). This condition is usually caused by dysfunction of the parathyroid glands, which are responsible for regulating calcium metabolism in the body. FHCH is most often inherited in an autosomal dominant pattern. Due to changes in the body's sensitivity to parathyroid hormone (PTH) and other factors associated with calcium metabolism, clinical manifestations of this condition may develop in the form of fatigue, muscle weakness, increased thirst, and type 2 diabetes. Note that this disease requires careful diagnosis and treatment to avoid potentially serious complications.
History of the disease and interesting historical facts
Familial hypocalciuric hypercalcemia was first described in the medical literature in the 1960s. Research at that time showed that the disorder of calcium metabolism can be hereditary. In 1996, it was discovered that hypocalciuric hypercalcemia is caused by a mutation in the CASR gene, which is responsible for encoding the calcium receptor. In the following decades, studies were conducted confirming the presence of various mutations of this gene in patients diagnosed with FHH. A number of cases were also recorded where this disease was observed in several members of the same family, which confirmed its hereditary nature.
Epidemiology
Familial hypocalciuric hypercalcemia is a rare disorder, but accurate statistics on its prevalence are limited. It is estimated to affect 1 to 4 people per 100,000 population, which creates the impression that there is a lack of relevant data to understand the scale of the problem. The disease can manifest itself at any age, but is most often diagnosed in young people or adults. Due to the autosomal dominant type of inheritance, the pathology is observed in both men and women equally.
Genetic predisposition to this disease
Familial hypocalciuric hypercalcemia is associated with mutations in the CASR gene, which codes for calcium receptors located on the surface of cells. This mutation leads to a decrease in the sensitivity of these cells to calcium, which in turn causes hypercalcemia, since the parathyroid glands continue to produce parathyroid hormone despite the discrepancy in calcium levels in the blood. In addition to CASR, genes involved may include GNA11 and AP2S1, which are also involved in the regulation of calcium metabolism. Inheritance of the disease occurs in an autosomal dominant manner, which means that one mutation in the gene of one parent is enough for the manifestation of symptoms of the disease in a child.
Risk factors for the development of this disease
Familial hypocalciuric hypercalcemia is primarily determined by genetic factors, but there are risk factors that may contribute to the development of the disease. These include:
- Heredity: presence of first-degree relatives with the disease.
- Age: Symptoms are more often observed in patients under 30 years of age.
- Genetic mutations: presence of specific mutations in genes such as CASR.
- Consumption of foods high in calcium: may increase hypercalcemia in susceptible patients.
Each of these factors can have a different impact on how quickly symptoms develop and the severity of the disease.
Diagnosis of this disease
Diagnosis of familial hypocalciuric hypercalcemia includes several stages:
- Main symptoms: Patients usually complain of fatigue, muscle weakness, increased thirst and frequent urination.
- Laboratory tests: detection of hypercalcemia (serum calcium level above 10.5 mg/dl), hypocalciuria (urinary calcium excretion less than 100 mg/day).
- Radiological tests: may help rule out other pathologies such as osteoporosis or tumor.
- Other types of diagnostics: molecular genetic testing to identify mutations in genes associated with the disease.
- Differential diagnosis: it is important to exclude primary hyperparathyroidism, sarcoidosis, malignant neoplasms with secondary hypercalcemia.
Correct diagnosis plays a critical role in choosing effective treatment.
Treatment
Treatment of familial hypocalciuric hypercalcemia should be comprehensive:
- General treatment: Lifestyle changes, including a diet restricted in calcium and phosphorus, require an individual approach.
- Pharmacological treatment: In some cases, calcitonin and bisphosphonates may be used to control calcium levels.
- Surgical treatment: indicated in the presence of other diseases of the parathyroid glands, such as adenoma or hyperplasia.
- Other treatments include drinking moderate amounts of fluids to lower the calcium levels in the blood.
It is important that the treatment is regulated by an experienced endocrinologist with post-laboratory control.
List of medications used to treat this disease
The following medications may be used to treat familial hypocalciuric hypercalcemia:
- Calcitonin.
- Bisphosphonates (eg, alendronate).
- Hormones that regulate calcium metabolism (for example, parathyroid hormone).
- Diuretics (thiazides) in some cases - to control calcium levels.
- Vitamin D restriction if necessary.
The appointment of appropriate therapy should only be carried out under the supervision of a specialist.
Disease monitoring
Monitoring the condition of a patient with familial hypocalciuric hypercalcemia requires regular observation:
- Control stages: tests for calcium levels in the blood and urine, assessment of kidney function, and the condition of the parathyroid glands.
- Prognosis: With timely and adequate therapy, the prognosis can be favorable. However, ignoring 症状 can lead to complications such as osteoporosis, kidney stones, and others.
- Complications: may arise as a consequence of the disease itself or as a result of incorrectly selected treatment.
Regular medical examinations significantly reduce the risk of complications.
Age-related features of the disease
Familial hypocalciuric hypercalcemia can occur in different age groups, but susceptibility to the disease and the severity of symptoms may vary:
- In children: often diagnosed at an early age, may have minor symptoms.
- In young people: symptoms often become more pronounced, phases of hypercalcemia may occur.
- In older people: symptoms may be less severe, but the risk of complications is significantly higher.
Depending on age, treatment approaches and prescriptions may vary.
Questions and Answers
- What causes familial hypocalciuric hypercalcemia?
The cause is mutations in genes associated with the regulation of calcium metabolism, most often in CASR. - What are the main symptoms of this disease?
The main symptoms include fatigue, muscle weakness, increased thirst and frequent urination. - How to diagnose hypercalcemia?
Diagnosis is made through laboratory tests, including serum calcium levels and urine analysis. - How is familial hypocalciuric hypercalcemia treated?
Treatment includes lifestyle changes, drug therapy, and, in rare cases, surgery. - What is the prognosis for patients with this disease?
The prognosis with adequate therapy is positive, but regular monitoring is necessary to prevent complications.
Advice from Dr. Oleg Korzhikov
If you have familial hypocalciuric hypercalcemia, it is important to monitor your lifestyle and undergo regular check-ups. I recommend monitoring your calcium levels and paying attention to any changes in your well-being. You also need to pay attention to your diet, excluding excessive consumption of calcium-rich foods. And, of course, follow the treatment prescribed by your doctor and do not ignore the prescribed control tests. Discuss all issues of interest to your doctor to avoid serious complications.
