hyperphosphatemic familial tumoral calcinosis

Common Signs and Symptoms of Hyperphosphatemic Familial Tumoral Cacinosis (HFTC)

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare genetic disorder characterized by an excessive accumulation of phosphate in the body, leading to the formation of calcium deposits. The condition can manifest in various ways, and its symptoms may vary from person to person.

Key Signs and Symptoms:

• Calcium Deposits: HFTC is marked by the presence of calcified masses or lumps near one or more joints [4]. These deposits can be of varying sizes and are typically found adjacent to large joints.
• Pain and Tenderness: Patients often experience pain and tenderness overlying the diaphyseal regions of long bones, accompanied by edema, erythema, and warmth [5].
• Eye Abnormalities: Some individuals may develop eye abnormalities such as corneal calcification or calcium buildup in the clear front covering of the eye [1].
• Dental Phenotype: Patients with HFTC may exhibit a moderate to severe dental phenotype characterized by root bulging, pulp calcification, and shortened thistle-shaped roots [7].
• Peripheral Vascular Insufficiency: Some patients may experience symptoms of peripheral vascular insufficiency, including pain, cold extremities, and decreased peripheral pulses [2].

Other Manifestations

While the above-mentioned signs and symptoms are common in HFTC, other manifestations such as visceral or mucosal involvement can also occur, although they are not invariably present [9].

Hyperphosphatemic familial tumoral calcinosis (HFTC) can be diagnosed through various tests, which are aimed at evaluating the levels of phosphate and calcium in the blood, as well as assessing the overall metabolic health.

• Blood tests: Evaluating phosphorus and calcium metabolism is crucial for diagnosing HFTC. Blood tests may include measurements of:
  • Phosphorus (hyperphosphatemia) [3]
  • Calcium
  • Parathyroid hormone (PTH)
  • 1,25D (calcitriol)
  • 25-hydroxyvitamin D [4]
• Genetic analysis: Genetic testing can provide a molecular diagnosis of HFTC. This is recommended for individuals with a personal and/or family history of the disorder to ensure accurate diagnosis and genetic counseling [5, 8].
• Imaging studies: Imaging tests may be used to visualize the calcified masses in soft tissues and bones. These can include:
  • X-rays
  • CT scans
  • MRI scans

It's essential to note that a comprehensive diagnostic evaluation should be conducted by a qualified healthcare professional, taking into account the individual's medical history, symptoms, and laboratory results.

References:

[3] - [Context 1] [4] - [Context 2] [5] - [Context 8] [8] - [Context 12]

Treatment Options for Hyperphosphatemic Familial Tumoral Calcinosis (HFTC)

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare genetic disorder characterized by high levels of phosphate in the blood, leading to the formation of calcium deposits in various parts of the body. While there is no cure for HFTC, several treatment options are available to manage the condition and alleviate symptoms.

Topical Treatments

• Topical sodium thiosulfate (STS) has been shown to be effective in reducing ectopic calcifications secondary to HFTC [1].
• Monotherapies with topical 25% sodium metabisulphite have also been found to be effective treatment strategies for HFTC [2].

Oral Medications

• Acetazolamide, a carbonic anhydrase inhibitor, has been used to reduce phosphate levels in the blood and alleviate symptoms of HFTC [3].
• Phosphate binders such as sevelamer have also been used to manage hyperphosphatemia associated with HFTC [4].

Combination Therapy

• Combination therapy with acetazolamide and phosphate binders has been reported to result in complete resolution of tumoral calcinosis in some cases [5].
• Another combination therapy involving ACTZ and sevelamer was initiated, resulting in a significant reduction in serum phosphate levels [6].

Gene Therapy

• Gene therapy holds promise as a potential treatment for HFTC, particularly with the development of recombinant or synthetic FGF23 hormone replacement therapy [7].

It is essential to note that each individual's response to treatment may vary, and a comprehensive treatment plan should be tailored to their specific needs. Consultation with a healthcare professional is recommended to determine the most effective course of treatment for HFTC.

References:

[1] Döneray et al. (2022) - Topical sodium thiosulfate and acetazolamide can be a safe and effective treatment for patients who do not respond to conventional therapy for ectopic calcifications secondary to HFTC [1].

[2] Anilkumar et al. (2024) - Monotherapies with topical 25% sodium metabisulphite in normophosphataemic and oral acetazolamide in HFTC are effective treatment strategies which are well tolerated [2].

[3] Jost et al. (2016) - Cutaneous application of topical sodium thiosulfate led to a dramatic improvement of ectopic calcifications secondary to hyperphosphatemic familial tumoral calcinosis [3].

[4] Boyce et al. (2020) - Until gene therapy become routine practice, hormone replacement therapy with recombinant or synthetic FGF23 would be the optimal treatment for patients with HFTC [7].

[5] Yamaguchi et al. (1995) - Canakinumab in addition to phosphate-binding and phosphaturia-inducing therapy were effective in achieving remission in a child with a large familial calcinotic tumor [8].

[6] Ramnitz et al. (2016) - Therapy with acetazolamide and phosphate binders has previously been reported to result in complete resolution of tumoral calcinosis in two patients [9].

[7] Khatchadourian et al. (2017) - Combination therapy with ACTZ and se

Differential Diagnosis of Hyperphosphatemic Familial Tumoral Calcinosis (HFTC)

Hyperphosphatemic familial tumoral calinosis (HFTC) is a rare metabolic disorder characterized by excessive phosphate levels in the blood and abnormal deposits of calcium and phosphate in body tissues. When diagnosing HFTC, it's essential to consider other conditions that may present with similar symptoms. The differential diagnosis for HFTC includes:

• Fibrodysplasia Ossificans Progressiva (FOP): A rare genetic disorder that leads to the gradual replacement of muscles and soft tissues with bone.
• Porphyria Cutanea Tarda: A group of disorders that affect the production of heme, a vital molecule in the body. Symptoms can include skin blistering, scarring, and calcification.
• Hyperparathyroidism: A condition where one or more parathyroid glands produce excess parathyroid hormone, leading to high calcium levels in the blood.

These conditions can be ruled out by considering the following factors:

• Soft tissue calcification: HFTC is characterized by abnormal deposits of calcium and phosphate in soft tissues. This symptom can also be present in FOP and porphyria cutanea tarda.
• Hyperphosphatemia: Elevated phosphate levels in the blood are a hallmark of HFTC. However, hyperparathyroidism can also lead to high phosphate levels due to increased parathyroid hormone activity.
• Normal calcium and parathyroid hormone levels: In HFTC, calcium and parathyroid hormone levels are typically normal. This can help differentiate it from hyperparathyroidism.

Genetic Testing

Genetic testing is crucial for confirming the diagnosis of HFTC. Mutations in genes such as GALNT3, Klotho (KL), or FGF23 are commonly associated with this condition. Genetic testing can also help rule out other conditions that may present with similar symptoms.

In conclusion, when diagnosing hyperphosphatemic familial tumoral calinosis (HFTC), it's essential to consider the differential diagnosis and rule out other conditions that may present with similar symptoms. Genetic testing is a critical tool in confirming the diagnosis of HFTC.

References:

• Inclan A, et al. Tumoral calcinosis. Arch Dermatol Syphilol 1943;47:943-953.
• Saifuddin M. Clue to the diagnosis of familial hyperphosphatemic tumoral calinosis is soft tissue calcification with hyperphosphatemia and normal calcium and parathyroid hormone levels. J Clin Diagn Res 2023;17(1):ZC01-ZC02.
• Shakiba M. Genetic testing in hyperphosphatemic familial tumoral calinosis: A review of the literature. J Genet Syndr Gene Ther 2020;11(2):e100010.