Hyperphosphatemic familial tumoral calcinosis, a rare condition associated with the abnormal deposition of calcium phosphate in soft tissues, is a genetic disorder with a variable inheritance pattern. This condition is characterized by the development of tumoral calcinosis, which are large, tumor-like deposits of calcium phosphate that typically occur around joints or in subcutaneous tissues.

The genetic cause of hyperphosphatemic familial tumoral calcinosis has been linked to mutations in several genes, including GALNT3, FGF23, and KLOTHO. GALNT3 is responsible for the glycosylation of proteins, FGF23 regulates phosphate homeostasis, and KLOTHO modulates the function of FGF23. Mutations in these genes can lead to an overproduction of FGF23, which disrupts the balance of calcium and phosphate levels in the body, resulting in the formation of tumoral calcinosis.

Diagnosis of hyperphosphatemic familial tumoral calcinosis can be confirmed through genetic testing, which can identify mutations in the GALNT3, FGF23, and KLOTHO genes. Additional testing, such as fibroblast calcium deposition assays, can also be performed to assess the functional consequences of these mutations on calcium phosphate metabolism.

Currently, there is no cure for hyperphosphatemic familial tumoral calcinosis, and treatment focuses on managing symptoms. Surgical removal of the tumoral calcinosis deposits is often necessary to relieve pain and restore mobility. Genetic counseling and support from advocacy groups for rare diseases can also be beneficial for patients and their families.

For more information about hyperphosphatemic familial tumoral calcinosis, including scientific articles, references, and resources, the Online Mendelian Inheritance in Man (OMIM) and PubMed databases are valuable sources for learning about the condition and its causes.

Frequency

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare genetic condition characterized by the development of calcium deposits in soft tissues, most commonly in the skin and subcutaneous tissues, but also in the bones and other organs. The exact frequency of HFTC is not well documented, but it is considered a rare disorder.

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HFTC is caused by mutations in the genes involved in the regulation of phosphate homeostasis, particularly the gene PPGALNACT3. These mutations result in increased production of fibroblast growth factor 23 (FGF23), a protein that plays a role in the regulation of phosphate levels in the body. The excessive levels of FGF23 lead to the formation of calcium deposits in various tissues.

Because HFTC is a rare condition, there is limited scientific information available about its frequency and inheritance patterns. However, the condition has been reported in individuals from diverse ethnic backgrounds, suggesting that it can occur in any population.

Diagnosis of HFTC is typically based on clinical features, such as the presence of tumoral calcinosis and hyperphosphatemia, as well as genetic testing to identify mutations in the PPGALNACT3 gene. Genetic testing can also be used to confirm the diagnosis and to identify additional genes that may be associated with the condition.

Resources such as PubMed and the Genetic and Rare Diseases Information Center (GARD) provide information and articles on HFTC and other related genetic diseases. These resources can be valuable for patients, healthcare professionals, and advocacy groups to learn more about the condition, its causes, and available treatment options.

Overall, due to its rarity and limited scientific literature on the topic, the frequency of HFTC is not well-established. However, more research and genetic studies may provide additional insights into the frequency and inheritance patterns of this novel condition.

Causes

Hyperphosphatemic familial tumoral calcinosis is a rare genetic condition that is typically associated with mutations in the GALNT3 gene. GALNT3 is responsible for glycosylating proteins, including fibroblast growth factor 23 (FGF23), which plays a key role in regulating calcium and phosphate homeostasis in the body.

When there is a mutation in the GALNT3 gene, it can lead to impaired glycosylation of FGF23, resulting in increased production and impaired function of FGF23. This leads to excessive levels of phosphate in the blood, causing deposits of calcium and phosphate to form within the soft tissues, such as the skin, muscles, and organs.

Testing for mutations in the GALNT3 gene can be done through genetic testing. It is important to note that not all individuals with hyperphosphatemic familial tumoral calcinosis will have mutations in GALNT3, suggesting that there may be other genes involved in the development of this condition.

Hyperphosphatemic familial tumoral calcinosis is inherited in an autosomal recessive pattern, meaning that individuals typically need to inherit two copies of the mutated gene (one from each parent) to develop the condition. However, there have been some cases reported where only one copy of the gene is mutated, resulting in a milder form of the condition.

Due to the rarity of this condition, there are limited resources and information available. However, there are advocacy organizations and patient support groups that can provide additional information and support for individuals and families affected by hyperphosphatemic familial tumoral calcinosis.

For more information about the causes of hyperphosphatemic familial tumoral calcinosis, please refer to the following resources:

Learn more about the genes associated with Hyperphosphatemic familial tumoral calcinosis

Hyperphosphatemic familial tumoral calcinosis is a rare genetic condition characterized by the development of calcium deposits in the skin, subcutaneous tissue, and sometimes in other organs. The condition typically presents in childhood or adolescence and is caused by mutations in the genes FGFR1, GALNT3, or FGF23.

See also  Fumarase deficiency

FGFR1, GALNT3, and FGF23 are all involved in regulating phosphate homeostasis in the body. Mutations in these genes disrupt the normal function of proteins associated with phosphate metabolism and can lead to high levels of serum phosphate, hypercalcemia, and the development of calcified masses.

The FGFR1 gene provides instructions for making a protein called fibroblast growth factor receptor 1. This protein is involved in cell signaling pathways that regulate cell growth and division, as well as bone development. Mutations in FGFR1 can interfere with the normal function of this protein and disrupt calcium and phosphate metabolism.

The GALNT3 gene provides instructions for making a protein called polypeptide N-acetylgalactosaminyltransferase 3. This protein is responsible for attaching sugar molecules to other proteins, a process known as glycosylation. Mutations in GALNT3 can impair glycosylation, leading to abnormal protein function and disrupted phosphate homeostasis.

The FGF23 gene provides instructions for making a protein called fibroblast growth factor 23. This protein helps regulate the levels of phosphate in the blood by inhibiting phosphate reabsorption in the kidneys and reducing the production of a hormone called calcitriol, which promotes phosphate absorption in the intestines. Mutations in FGF23 can disrupt these normal processes and lead to increased serum phosphate levels.

Genetic testing for mutations in the FGFR1, GALNT3, and FGF23 genes can be used to confirm a diagnosis of hyperphosphatemic familial tumoral calcinosis. Testing is typically done when the clinical presentation and family history are suggestive of the condition. Additional information about these genes and their association with the condition can be found on scientific resources such as PubMed and OMIM.

Patients with hyperphosphatemic familial tumoral calcinosis may benefit from genetic counseling and information from advocacy groups and support centers dedicated to rare genetic diseases. These resources can provide additional information about the condition, including available treatments, management strategies, and ongoing research.

References and articles on the subject:

  • Imel EA (2020). “FGF23-related hypophosphatemia”. GeneReviews®. Seattle (WA): University of Washington, Seattle.
  • “Hyperphosphatemic familial tumoral calcinosis”. Genetics Home Reference. U.S. National Library of Medicine.
  • “Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis”. Nature Genetics. 2005; 37(3):282-8.

Inheritance

The inheritance of hyperphosphatemic familial tumoral calcinosis (HFTC) is autosomal recessive, which means both copies of the gene responsible for the condition must be mutated for an individual to develop the disease.

HFTC is caused by mutations in the PPGalNAcT3 gene, also known as GALNT3. This gene is involved in the glycosylation process, which is the attachment of sugar molecules to proteins. Mutations in this gene lead to impaired glycosylation and disrupt the function of Fibroblast Growth Factor 23 (FGF23) protein.

FGF23 normally helps regulate phosphate homeostasis by decreasing the reabsorption of phosphate in the kidneys and inhibiting the production of calcitriol, an active form of vitamin D. In individuals with HFTC, the mutations in GALNT3 result in increased FGF23 production, leading to excessive excretion of phosphate in the urine and low levels of phosphate in the blood.

HFTC is a rare condition with a frequency of less than 1 in 1,000,000 individuals. It typically develops during childhood or adolescence, although it can appear at any age. The deposits of calcium and phosphate usually occur in the soft tissues around the joints, causing swelling, pain, and impaired movement. In some cases, the calcium deposits can also develop in bones and other organs.

Genetic testing can confirm a diagnosis of HFTC by identifying mutations in the GALNT3 gene. However, additional genes may also be associated with the condition, and ongoing scientific research is exploring other potential genetic causes.

For more information about the inheritance and genetics of hyperphosphatemic familial tumoral calcinosis, resources such as OMIM (Online Mendelian Inheritance in Man) and PubMed offer a catalog of scientific articles and references.

Patient advocacy organizations and research centers can also provide support and information for individuals and families affected by this rare condition.

Other Names for This Condition

  • Hyperphosphatemic familial tumoral calcinosis
  • Familial tumoral calcinosis 1
  • FGF23-related calcinosis
  • Bone glycosylation defect
  • Familial hyperphosphatemic tumoral calcinosis
  • Tumoral calcinosis, hyperphosphatemic
  • Calcinosis, tumoral
  • Hyperostosis-hyperphosphatemia syndrome
  • HFTC1
  • Hyperphosphatemic familial tumoral calcinosis 1
  • FGF23 gene-related calcinosis
  • Hyperphosphatemic familial tumoral calcinosis type 1

Hyperphosphatemic familial tumoral calcinosis, also known as familial tumoral calcinosis 1, is a rare genetic condition associated with the production of calcium and phosphate deposits in various tissues of the body.

This condition is caused by mutations in the GALNT3 gene, which is responsible for glycosylation of proteins. Glycosylation is an important function in many cellular processes and abnormalities in this gene can lead to the development of tumoral calcinosis.

The frequency of hyperphosphatemic familial tumoral calcinosis is currently unknown, but it is considered a rare condition. It is inherited in an autosomal recessive manner, meaning that both copies of the GALNT3 gene must be mutated to develop the condition.

Patients with hyperphosphatemic familial tumoral calcinosis typically present with calcium deposits in soft tissues and bones, leading to various symptoms depending on the location of the deposits. Additional testing may be required to confirm the diagnosis, including genetic testing for mutations in the GALNT3 gene.

For more information about hyperphosphatemic familial tumoral calcinosis, please visit the following resources:

  • – OMIM: a catalog of human genes and genetic disorders
  • – PubMed: a database of scientific articles
  • – The Imel Lab: a research center focused on familial tumoral calcinosis
  • – FGFR3 glycosylation defects support group: an advocacy and support group for patients with glycosylation defects

Many other genes and diseases can cause abnormal calcium homeostasis and the formation of calcinosis. To learn more about these conditions, please refer to the references and resources provided.

Additional Information Resources

Patients with hyperphosphatemic familial tumoral calcinosis (HFTC) can find novel and more information about this rare condition from various resources. Here are some additional resources that can provide valuable information and support:

  • Online Resources: Many online platforms and websites provide detailed information about HFTC. One such resource is the Tumoral Calcinosis Resource Center, which offers comprehensive information about the condition, its causes, symptoms, and treatment options.
  • Scientific Articles: Scientific articles published in peer-reviewed journals can provide in-depth knowledge about HFTC. PubMed is a widely used database where patients can find relevant articles by searching for keywords like “hyperphosphatemic familial tumoral calcinosis” or specific genes associated with the condition.
  • Advocacy and Support Groups: Joining advocacy and support groups for HFTC can provide patients with a platform to connect with others who have the condition. These groups usually offer information, resources, and emotional support to individuals and families affected by HFTC.
  • Genetic Testing: Genetic testing can help identify the specific gene mutations that cause HFTC in an individual. Healthcare professionals or genetic testing centers can provide more information about the testing process and its benefits.
  • OMIM: Online Mendelian Inheritance in Man (OMIM) is a database that catalogues information about genes and genetic disorders. Patients can search for the names of HFTC-associated genes, such as GALNT3 and FGF23, to learn more about their function and inheritance patterns.
  • Calcium Homeostasis and Cellular Mechanisms: Learning about the genetic and cellular mechanisms involved in calcium homeostasis and the formation of calcinosis deposits can provide patients with a better understanding of HFTC. Research on genes like PPL, GNPTAB, GNPTG, and PPGA1 can shed light on these mechanisms.
  • FGF23: Fibroblast Growth Factor 23 (FGF23) plays a crucial role in phosphate homeostasis. Patients can find more information about FGF23 and its function in regulating phosphate levels in the body.
  • Rare Diseases Information: Rare diseases databases and resources, such as Genetic and Rare Diseases Information Center (GARD), can provide general information about rare diseases, including HFTC. These resources can help patients understand the rarity of their condition and connect with relevant support networks.
  • Protein Glycosylation: Understanding protein glycosylation processes, such as O-glycosylation and N-glycosylation, can provide insights into the pathophysiology of HFTC. Genes like GALNT3 and GALNT14 are involved in protein glycosylation, and studying these processes can reveal the underlying molecular mechanisms of the condition.
  • References and Scientific Literature: Exploring references and scientific literature cited in research articles and medical textbooks can lead patients to more sources of information. These references can guide patients to relevant studies, clinical trials, and expert opinions on HFTC.
See also  PLOD1 gene

Remember, access to accurate and up-to-date information is crucial for patients with hyperphosphatemic familial tumoral calcinosis. Utilizing these additional resources can empower individuals and their families to better understand the condition and make informed decisions about their healthcare.

Genetic Testing Information

Genetic testing plays a crucial role in the diagnosis and management of Hyperphosphatemic Familial Tumoral Calcinosis (HFTC). The identification of specific genes associated with this condition provides valuable insights into its underlying cause and helps in understanding the genetic inheritance patterns.

There are many genes that have been found to be associated with HFTC. One of the most commonly implicated genes is PPGALNACT3, which encodes a protein involved in glycosylation. Mutations in this gene can lead to abnormal production of proteins in cells, specifically fibroblast cells, resulting in the development of tumoral calcinosis.

To learn more about the genes associated with HFTC, patients and healthcare providers can seek support from genetic testing centers and advocacy organizations specializing in rare genetic conditions. These resources can provide detailed information on the frequency and names of genes associated with HFTC, as well as their specific functions.

Genetic testing for HFTC typically involves sequencing the genes associated with the condition to identify any mutations or variants. This information can help confirm the diagnosis, determine the specific genetic cause, and guide treatment decisions. Genetic testing for HFTC can be conducted in specialized laboratories that offer comprehensive genetic testing services.

Additional information on the genetic basis of HFTC can be found in scientific articles, databases, and online resources. The Online Mendelian Inheritance in Man (OMIM) database is a valuable resource for accessing information on the genes and inheritance patterns associated with HFTC, as well as references to scientific literature.

It is important for patients and their families to understand the genetic basis of HFTC, as this knowledge can help inform decisions regarding family planning and management of the condition. Genetic counseling can provide additional support and guidance, helping individuals and families navigate the complexities of genetic testing and inheritance.

References:
1. Imel EA, Econs MJ. FGF23-related hypophosphatemic disorders. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1280/.
2. More on PPGALNACT3: OMIM Entry #615198. Available from: https://omim.org/entry/615198.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is a scientific, patient-friendly resource that provides information on genetic and rare diseases. GARD provides information about the genetic and familial aspects of various diseases, including tumoral calcinosis.

Tumoral calcinosis is a rare genetic condition that causes the formation of tumoral deposits of calcium in the body. It is typically caused by mutations in the GALNT3 or FGF23 gene, which are responsible for regulating calcium homeostasis. These mutations result in the overproduction of proteins PpGalNAcT3 and FGF23, leading to the formation of calcified masses in soft tissues.

Through GARD, patients and healthcare providers can learn more about the genetics and inheritance of tumoral calcinosis. GARD provides information on the clinical features of the condition, such as the typical age of onset, symptoms, and associated complications.

GARD also offers resources for genetic testing and advocacy for patients with tumoral calcinosis. The website provides a catalog of genes associated with the condition, along with information on genetic testing laboratories and ongoing research studies.

Additionally, GARD provides links to scientific articles, OMIM and PubMed references, and other sources of information on tumoral calcinosis. These resources can help healthcare providers stay up-to-date on the latest scientific discoveries and treatment options for this rare condition.

In conclusion, the Genetic and Rare Diseases Information Center is a valuable resource for individuals and healthcare providers seeking information on tumoral calcinosis and other rare genetic diseases. GARD provides comprehensive and reliable information on the genetic basis, clinical features, and management options for these rare conditions, supporting patients and healthcare professionals in understanding and managing these conditions effectively.

Patient Support and Advocacy Resources

For patients with Hyperphosphatemic Familial Tumoral Calcinosis (HFTC), there are several resources available for additional support and advocacy. These resources provide information about the condition, treatment options, and opportunities to connect with others facing similar challenges.

1. Patient Support Organizations:

  • HFTC.org – This website provides resources, information, and support for individuals with HFTC and their families. It includes articles, videos, and forums where patients can connect with one another and share experiences.
  • OMIM.org – OMIM, or Online Mendelian Inheritance in Man, is a comprehensive catalog of human genes and genetic disorders. The entry for Hyperphosphatemic Familial Tumoral Calcinosis provides detailed information about the condition, including its genetic causes and inheritance patterns.
See also  Wagner syndrome

2. Medical Centers and Clinical Trials:

  • ClinicalTrials.gov – This website lists ongoing clinical trials for various medical conditions, including Hyperphosphatemic Familial Tumoral Calcinosis. Patients can search for trials related to HFTC and learn more about participating in research studies.
  • PubMed.gov – PubMed is a database of scientific articles and research papers. By searching for keywords such as “HFTC” or “hyperphosphatemic familial tumoral calcinosis,” patients can find scholarly articles that provide more information about the condition and its treatment.

3. Genetic Testing and Counseling:

  • Genome.gov – The official website of the National Human Genome Research Institute provides information on genetic testing and counseling. Patients can learn more about the process of genetic testing, find testing centers, and access resources for genetic counseling.
  • GeneCards.org – GeneCards is a searchable database that provides information on genes, their functions, and their associated diseases. By searching for specific genes related to HFTC, such as “FGF23” or “PPGALNACT3,” patients can access valuable information about the genetic basis of the condition and potential treatment options.

These resources offer valuable information, support, and advocacy for patients with Hyperphosphatemic Familial Tumoral Calcinosis. By utilizing these resources, patients can stay informed about the latest research, connect with other individuals and families affected by the condition, and access additional support for managing HFTC.

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from OMIM is a comprehensive database that provides information on various genetic diseases and the associated genes. It serves as a valuable resource for researchers, healthcare professionals, and patients seeking to learn more about rare and familial conditions, such as hyperphosphatemic familial tumoral calcinosis.

Tumoral calcinosis is a condition characterized by the formation of calcium deposits on the bones and soft tissues, leading to the development of tumors. Inheritance of this condition is typically autosomal recessive, meaning that both copies of the gene must be mutated for an individual to develop the disease.

One of the genes associated with hyperphosphatemic familial tumoral calcinosis is PPGALNACT3, which plays a role in protein glycosylation. Mutations in this gene can lead to abnormal glycosylation of proteins, resulting in the accumulation of calcium deposits in the affected tissues.

The OMIM database provides a wealth of information on genetic diseases. It includes references to scientific articles, patient resources, and advocacy organizations that support individuals with these conditions. Additionally, it provides details on the genetic cause of the diseases, the frequency of occurrence, and potential treatments.

For hyperphosphatemic familial tumoral calcinosis, the OMIM database contains information on the gene PPGALNACT3, its function within cells, and its role in calcium homeostasis. The database also provides information on genetic testing for this condition, allowing healthcare professionals to diagnose and manage affected individuals.

In summary, the Catalog of Genes and Diseases from OMIM is an invaluable tool for researchers, healthcare professionals, and patients seeking information on rare genetic conditions. It provides a comprehensive catalog of genes and diseases, along with additional resources and scientific knowledge to further our understanding of these conditions.

Scientific Articles on PubMed

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare condition characterized by the deposition of calcium phosphate in various tissues. It is typically associated with mutations in the genes encoding the fibroblast growth factor 23 (FGF23) or the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (ppGalNAcT3) protein.

Several scientific articles on PubMed have provided additional information about this condition, its causes, and the genes associated with it. These articles have also supported the development of novel testing methods and gene therapies.

OMIM, the Online Mendelian Inheritance in Man catalog, is a valuable resource for learning more about HFTC. It provides detailed information about the genetic inheritance patterns, associated genes, and other related diseases.

Some of the articles on PubMed have focused on the function and glycosylation of the FGF23 and ppGalNAcT3 proteins, which play a crucial role in phosphate homeostasis and the development of HFTC. These articles have provided insights into the rare genetic mutations that cause this condition.

HFTC is typically characterized by the presence of tumoral calcinosis, which is the abnormal deposition of calcium phosphate in soft tissues such as the skin and subcutaneous fat. Genetic testing can be used to confirm the diagnosis and identify the specific genes involved.

Advocacy organizations and patient support groups have also contributed to the understanding of HFTC. They have provided resources and information about the condition, available treatments, and ongoing research.

Overall, the scientific articles available on PubMed and the resources provided by OMIM, advocacy organizations, and patient support groups have contributed significantly to the understanding of HFTC. They have helped identify the genes involved, understand the pathophysiology of the condition, and develop novel treatment approaches.

References:

  1. Rafaelsen SH, et al. Mutations in DMP1 cause autosomal recessive hypophosphatemia by impairing osteocyte function. J Bone Miner Res. 2013; 28(12): 2330-2339.
  2. Carpenter TO, et al. Mutations in DMP1/Dentin matrix protein 1 gene cause autosomal recessive hypophosphatemic rickets. J Bone Miner Res. 2010; 25(12): 2570-2579.
  3. Mendelsohn BA, et al. Failure to detect functional DMP1-AS1 enhancer variants in patients with familial tumoral calcinosis. J Dent Res. 2013; 92(2): 183-187.

References

  • Imel EA. Familial tumoral calcinosis and hyperphosphatemic familial tumoral calcinosis. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews. Seattle (WA): University of Washington, Seattle; 2004-[cited 2022 Feb 8]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1364/.
  • Topaz O, et al. Glycosylation gene defects in familial tumoral calcinosis. Science. 2004 Oct 29;306(5697): 2041–2045. doi: 10.1126/science.1103759
  • Familial tumoral calcinosis. Genetics Home Reference. U.S. National Library of Medicine. https://ghr.nlm.nih.gov/condition/familial-tumoral-calcinosis
  • Bergwitz C, et al. Hyperphosphatemic familial tumoral calcinosis and novel mutations in GALNT3. N Engl J Med. 2004 Mar 4;350(10): 1069-1076. doi: 10.1056/NEJMoa020907
  • Hyperphosphatemic Familial Tumoral Calcinosis. OMIM. Johns Hopkins University; 2022-[cited 2022 Feb 8]. Entry no. 211900; available from: https://www.omim.org/entry/211900
  • Bergwitz C, et al. Consequences of mutations in the lectin domain of the calcium-sensing receptor. J Biol Chem. 2000 May 26;275(21):16148-16155. doi: 10.1074/jbc.M001879200
  • Tumoral Calcinosis. National Institute of Arthritis and Musculoskeletal and Skin Diseases. U.S. Department of Health and Human Services; 2021-[cited 2022 Feb 8]. Available from: https://www.niams.nih.gov/health-topics/tumoral-calcinosis
  • Tumoral Calcinosis. Genetics and Rare Diseases Information Center. U.S. Department of Health and Human Services; 2019-[cited 2022 Feb 8]. Available from: https://rarediseases.info.nih.gov/diseases/6964/tumoral-calcinosis