MCID: TMR011
MIFTS: 48

Tumoral Calcinosis, Hyperphosphatemic, Familial

Categories: Genetic diseases, Rare diseases, Skin diseases, Metabolic diseases, Endocrine diseases

Aliases & Classifications for Tumoral Calcinosis, Hyperphosphatemic, Familial

MalaCards integrated aliases for Tumoral Calcinosis, Hyperphosphatemic, Familial:

Name: Tumoral Calcinosis, Hyperphosphatemic, Familial 54 50 71 69
Hftc 12 50 25 71
Hyperphosphatemic Familial Tumoral Calcinosis 12 50 25
Cortical Hyperostosis with Hyperphosphatemia 12 50 71
Hyperostosis-Hyperphosphatemia Syndrome 50 71 69
Tumoral Calcinosis, Hyperphosphatemic 54 13 52
Hyperostosis with Hyperphosphatemia 12 50 71
Hhs 12 50 71
Familial Hyperphosphatemic Tumoral Calcinosis/hyperphosphatemic Hyperostosis Syndrome 12 56
Primary Hyperphosphatemic Tumoral Calcinosis 12 25
Hyperphosphatemia Hyperostosis Syndrome 12 25
Hyperphosphatemia Tumoral Calcinosis 12 25
Hypercalcemic Tumoral Calcinosis 12 56
Hyperphosphatemia Hyperostosis 12 25
Lipocalcinogranulomatosis 12 71
Morbus Teutschlaender 12 71
Phptc 12 71
Familial Tumoral Calcinosis with Hyperphosphatemia 71
Tumoral Calcinosis, Familial, Hyperphosphatemic 29
Tumoral Calcinosis Primary Hyperphosphatemic 71
Tumoral Calcinosis with Hyperphosphatemia 12
Familial Teutschlaender Disease 12
Teutschlaender Disease 71
Tumoral Calcinosis 69

Characteristics:

Orphanet epidemiological data:

56

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in first decade of life
variable manifestations
high prevalence among individuals of middle eastern or african descent
heterozygote may have elevated serum phosphate and elevated serum 1,25-dihydroxycholecalciferol


HPO:

32
tumoral calcinosis, hyperphosphatemic, familial:
Inheritance autosomal recessive inheritance
Onset and clinical course juvenile onset


Classifications:



Summaries for Tumoral Calcinosis, Hyperphosphatemic, Familial

OMIM : 54
Hyperphosphatemic familial tumoral calcinosis is a rare autosomal recessive metabolic disorder characterized by the progressive deposition of basic calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone (Chefetz et al., 2005). The biochemical hallmark of tumoral calcinosis is hyperphosphatemia caused by increased renal absorption of phosphate due to loss-of-function mutations in the FGF23 or GALNT3 gene. The term 'hyperostosis-hyperphosphatemia syndrome' is sometimes used when the disorder is characterized by involvement of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis. Although some have distinguished HHS from FTC by the presence of bone involvement and the absence of skin involvement (Frishberg et al., 2005), Ichikawa et al. (2010) concluded that the 2 entities represent a continuous spectrum of the same disease, best described as familial hyperphosphatemic tumoral calcinosis. HFTC is considered to be the clinical converse of autosomal dominant hypophosphatemic rickets (ADHR; 193100), an allelic disorder caused by gain-of-function mutations in the FGF23 gene and associated with hypophosphatemia and decreased renal phosphate absorption (Chefetz et al., 2005; Ichikawa et al., 2005). (211900)

MalaCards based summary : Tumoral Calcinosis, Hyperphosphatemic, Familial, also known as hftc, is related to calcinosis and hyperphosphatemic familial tumoral calcinosis, fgf23-related, and has symptoms including nephrocalcinosis, hyperphosphatemia and pulp stones. An important gene associated with Tumoral Calcinosis, Hyperphosphatemic, Familial is FGF23 (Fibroblast Growth Factor 23), and among its related pathways/superpathways are mTOR signalling and Negative regulation of FGFR1 signaling. The drugs Sevelamer and Alfacalcidol have been mentioned in the context of this disorder. Affiliated tissues include skin, bone and brain, and related phenotypes are digestive/alimentary and integument

Disease Ontology : 12 A calcinosis characterized by autosomal recessive inheritance of elevated blood calcium levels and calcium phosphate crystals in cutaneous and subcutaneous tissues that has material basis in mutation in the GALNT3 gene, the FGF23 gene, or the KL gene.

Genetics Home Reference : 25 Hyperphosphatemic familial tumoral calcinosis (HFTC) is a condition characterized by an increase in the levels of phosphate in the blood (hyperphosphatemia) and abnormal deposits of phosphate and calcium (calcinosis) in the body's tissues. Calcinosis typically develops in early childhood to early adulthood, although in some people the deposits first appear in infancy or in late adulthood. Calcinosis usually occurs in and just under skin tissue around the joints, most often the hips, shoulders, and elbows. Calcinosis may also develop in the soft tissue of the feet, legs, and hands. Rarely, calcinosis occurs in blood vessels or in the brain and can cause serious health problems. The deposits develop over time and vary in size. Larger deposits form masses that are noticeable under the skin and can interfere with the function of joints and impair movement. These large deposits may appear tumor-like (tumoral), but they are not tumors or cancerous. The number and frequency of deposits varies among affected individuals; some develop few deposits during their lifetime, while others may develop many in a short period of time.

UniProtKB/Swiss-Prot : 71 Tumoral calcinosis, hyperphosphatemic, familial: A severe metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Some patients manifest recurrent, transient, painful swellings of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis and absence of skin involvement.

Related Diseases for Tumoral Calcinosis, Hyperphosphatemic, Familial

Diseases in the Tumoral Calcinosis, Hyperphosphatemic, Familial family:

Hyperphosphatemic Familial Tumoral Calcinosis, Fgf23-Related Hyperphosphatemic Familial Tumoral Calcinosis, Galnt3-Related
Hyperphosphatemic Familial Tumoral Calcinosis, Kl-Related

Diseases related to Tumoral Calcinosis, Hyperphosphatemic, Familial via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 69)
id Related Disease Score Top Affiliating Genes
1 calcinosis 28.5 FGF23 KL
2 hyperphosphatemic familial tumoral calcinosis, fgf23-related 12.2
3 hyperphosphatemic familial tumoral calcinosis, galnt3-related 12.2
4 hyperphosphatemic familial tumoral calcinosis, kl-related 12.2
5 hypotrichosis 1 11.5
6 dyskeratosis congenita, x-linked 11.4
7 heart-hand syndrome, slovenian type 11.3
8 hyperinsulinism-hyperammonemia syndrome 11.3
9 hypogonadotropic hypogonadism 7 without anosmia 11.3
10 hemochromatosis 11.2
11 hypogonadotropic hypogonadism 11.0
12 hypothalamic hamartomas, somatic 10.9
13 hypogonadotropic hypogonadism 2 with or without anosmia 10.8
14 dyskeratosis congenita, autosomal dominant 1 10.8
15 dyskeratosis congenita, autosomal recessive 5 10.8
16 kallmann syndrome 10.8
17 hypotrichosis simplex 10.7
18 hypogonadotropic hypogonadism 20 with or without anosmia 10.6
19 hypogonadotropic hypogonadism 12 with or without anosmia 10.6
20 hypogonadotropic hypogonadism 13 with or without anosmia 10.6
21 hypogonadotropic hypogonadism 5 with or without anosmia 10.6
22 hypogonadotropic hypogonadism 9 with or without anosmia 10.6
23 hypogonadotropic hypogonadism 15 with or without anosmia 10.6
24 hypogonadotropic hypogonadism 6 with or without anosmia 10.6
25 hypogonadotropic hypogonadism 14 with or without anosmia 10.6
26 hypogonadotropic hypogonadism 4 with or without anosmia 10.6
27 hypogonadotropic hypogonadism 10 with or without anosmia 10.6
28 hypogonadotropic hypogonadism 18 with or without anosmia 10.6
29 hypogonadotropic hypogonadism 19 with or without anosmia 10.6
30 hypogonadotropic hypogonadism 11 with or without anosmia 10.6
31 hypogonadotropic hypogonadism 8 with or without anosmia 10.6
32 hypogonadotropic hypogonadism 17 with or without anosmia 10.6
33 hypogonadotropic hypogonadism 3 with or without anosmia 10.6
34 hypogonadotropic hypogonadism 21 with anosmia 10.6
35 hypogonadotropic hypogonadism 16 with or without anosmia 10.6
36 hypogonadotropic hypogonadism 22, with or without anosmia 10.6
37 familial tumoral calcinosis 10.0
38 peroxisome biogenesis disorder 2a 9.8 FGF23 GALNT3
39 hypogonadotropism 9.8
40 hyperphosphatemia 9.8
41 breast cancer 9.8
42 hypogonadism 9.8
43 hyperostosis 9.8
44 atelosteogenesis 9.8 FGF23 GALNT3
45 hiv-1 9.7
46 pancreatitis 9.7
47 lung cancer 9.7
48 hepatitis 9.7
49 hepatocellular carcinoma 9.7
50 autism spectrum disorder 9.7

Graphical network of the top 20 diseases related to Tumoral Calcinosis, Hyperphosphatemic, Familial:



Diseases related to Tumoral Calcinosis, Hyperphosphatemic, Familial

Symptoms & Phenotypes for Tumoral Calcinosis, Hyperphosphatemic, Familial

Symptoms via clinical synopsis from OMIM:

54

Laboratory- Abnormalities:
normal serum calcium
hyperphosphatemia
normal to elevated serum 1,25-dihydroxycholecalciferol (calcitriol)
increased serum fgf23
normal serum parathyroid hormone (pth)
more
Head And Neck- Teeth:
obliterated tooth pulp cavities
pulp stones
thin dental enamel
disturbed root development
short blunt tooth roots
more
Genitourinary- Kidneys:
increased renal tubular phosphate reabsorption
decreased renal tubular phosphate excretion
calcinosis of the renal parenchyma

Skeletal- Limbs:
painful swellings of the long bones, acute, recurrent attacks
cortical hyperostosis
periosteal reaction
diaphysitis
radiography shows porotic changes
more
Head And Neck- Eyes:
angioid streaks, retina
conjunctival irritation
conjunctival whitish 'salt-like' deposits

Cardiovascular- Vascular:
vascular calcifications

Skeletal:
tumoral calcinosis
ectopic periarticular calcified masses, painful (hip, elbow, shoulder)
progressive deposition of basic calcium phosphate crystals

Skin Nails & Hair- Skin:
deposition of calcium phosphate crystals in skin and subcutaneous tissues


Clinical features from OMIM:

211900

Human phenotypes related to Tumoral Calcinosis, Hyperphosphatemic, Familial:

32 (show all 12)
id Description HPO Frequency HPO Source Accession
1 nephrocalcinosis 32 HP:0000121
2 hyperphosphatemia 32 HP:0002905
3 pulp stones 32 HP:0003771
4 increased renal tubular phosphate reabsorption 32 HP:0005571
5 decreased renal tubular phosphate excretion 32 HP:0005572
6 angioid streaks of the retina 32 HP:0001102
7 calcinosis 32 HP:0003761
8 taurodontia 32 HP:0000679
9 abnormality of the skin 32 HP:0000951
10 hypoplasia of dental enamel 32 HP:0006297
11 vascular calcification 32 HP:0004934
12 conjunctival whitish salt-like deposits 32 HP:0007799

MGI Mouse Phenotypes related to Tumoral Calcinosis, Hyperphosphatemic, Familial:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.43 FGF23 GALNT3 KL
2 integument MP:0010771 9.33 FGF23 GALNT3 KL
3 limbs/digits/tail MP:0005371 9.13 FGF23 GALNT3 KL
4 renal/urinary system MP:0005367 8.8 FGF23 GALNT3 KL

Drugs & Therapeutics for Tumoral Calcinosis, Hyperphosphatemic, Familial

Drugs for Tumoral Calcinosis, Hyperphosphatemic, Familial (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 8)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Sevelamer Approved 52757-95-6, 152751-57-0 3085017
2
Alfacalcidol Approved, Nutraceutical 41294-56-8 5282181
3 Bone Density Conservation Agents
4 Chelating Agents
5 Hydroxycholecalciferols
6 Micronutrients
7 Trace Elements
8 Vitamins

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Hypophosphatemic Rickets in Norway Active, not recruiting NCT01057186 Sevelamer

Search NIH Clinical Center for Tumoral Calcinosis, Hyperphosphatemic, Familial

Genetic Tests for Tumoral Calcinosis, Hyperphosphatemic, Familial

Genetic tests related to Tumoral Calcinosis, Hyperphosphatemic, Familial:

id Genetic test Affiliating Genes
1 Tumoral Calcinosis, Familial, Hyperphosphatemic 29

Anatomical Context for Tumoral Calcinosis, Hyperphosphatemic, Familial

MalaCards organs/tissues related to Tumoral Calcinosis, Hyperphosphatemic, Familial:

39
Skin, Bone, Brain, Retina

Publications for Tumoral Calcinosis, Hyperphosphatemic, Familial

Variations for Tumoral Calcinosis, Hyperphosphatemic, Familial

UniProtKB/Swiss-Prot genetic disease variations for Tumoral Calcinosis, Hyperphosphatemic, Familial:

71
id Symbol AA change Variation ID SNP ID
1 FGF23 p.Ser71Gly VAR_023831 rs104894342
2 FGF23 p.Met96Thr VAR_071711 rs104894343
3 FGF23 p.Ser129Phe VAR_071712 rs104894344
4 FGF23 p.Phe157Leu VAR_071713 rs772964687
5 KL p.His193Arg VAR_064554 rs121908423

ClinVar genetic disease variations for Tumoral Calcinosis, Hyperphosphatemic, Familial:

6 (show all 17)
id Gene Variation Type Significance SNP ID Assembly Location
1 FGF23 NM_020638.2(FGF23): c.287T> C (p.Met96Thr) single nucleotide variant Pathogenic rs104894343 GRCh37 Chromosome 12, 4481788: 4481788
2 FGF23 NM_020638.2(FGF23): c.386C> T (p.Ser129Phe) single nucleotide variant Pathogenic rs104894344 GRCh37 Chromosome 12, 4479879: 4479879
3 KL NM_004795.3(KL): c.578A> G (p.His193Arg) single nucleotide variant Pathogenic rs121908423 GRCh37 Chromosome 13, 33591156: 33591156
4 GALNT3 NM_004482.3(GALNT3): c.1524+1G> A single nucleotide variant Pathogenic rs745655924 GRCh38 Chromosome 2, 165754931: 165754931
5 GALNT3 NM_004482.3(GALNT3): c.484C> T (p.Arg162Ter) single nucleotide variant Pathogenic rs137853086 GRCh37 Chromosome 2, 166626727: 166626727
6 GALNT3 NM_004482.3(GALNT3): c.1524+5G> A single nucleotide variant Pathogenic rs375879489 GRCh38 Chromosome 2, 165754927: 165754927
7 GALNT3 NM_004482.3(GALNT3): c.516_688del single nucleotide variant Pathogenic rs761396172 GRCh38 Chromosome 2, 165765058: 165765058
8 GALNT3 NM_004482.3(GALNT3): c.1774C> T (p.Gln592Ter) single nucleotide variant Pathogenic rs137853087 GRCh37 Chromosome 2, 166606257: 166606257
9 GALNT3 NM_004482.3(GALNT3): c.1076C> A (p.Thr359Lys) single nucleotide variant Pathogenic rs137853091 GRCh37 Chromosome 2, 166615372: 166615372
10 GALNT3 NM_004482.3(GALNT3): c.966T> G (p.Tyr322Ter) single nucleotide variant Pathogenic rs137853088 GRCh37 Chromosome 2, 166615953: 166615953
11 GALNT3 NM_004482.3(GALNT3): c.1441C> T (p.Gln481Ter) single nucleotide variant Pathogenic rs137853089 GRCh37 Chromosome 2, 166611525: 166611525
12 GALNT3 NM_004482.3(GALNT3): c.815C> A (p.Thr272Lys) single nucleotide variant Pathogenic rs137853090 GRCh37 Chromosome 2, 166618438: 166618438
13 GALNT3 NM_004482.3(GALNT3): c.803dupC (p.Thr269Asnfs) duplication Pathogenic rs766750282 GRCh37 Chromosome 2, 166618450: 166618450
14 GALNT3 NM_004482.3(GALNT3): c.1525_1626del single nucleotide variant Pathogenic rs760830864 GRCh38 Chromosome 2, 165754626: 165754626
15 GALNT3 NM_004482.3(GALNT3): c.677delC (p.Ala226Valfs) deletion Pathogenic rs786205250 GRCh37 Chromosome 2, 166621405: 166621405
16 GALNT3 NM_004482.3(GALNT3): c.1720T> G (p.Cys574Gly) single nucleotide variant Pathogenic rs267606841 GRCh37 Chromosome 2, 166606311: 166606311
17 FGF23 NM_020638.2(FGF23): c.260G> A (p.Gly87Asp) single nucleotide variant Likely pathogenic rs863224872 GRCh38 Chromosome 12, 4372649: 4372649

Expression for Tumoral Calcinosis, Hyperphosphatemic, Familial

Search GEO for disease gene expression data for Tumoral Calcinosis, Hyperphosphatemic, Familial.

Pathways for Tumoral Calcinosis, Hyperphosphatemic, Familial

GO Terms for Tumoral Calcinosis, Hyperphosphatemic, Familial

Biological processes related to Tumoral Calcinosis, Hyperphosphatemic, Familial according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 MAPK cascade GO:0000165 9.43 FGF23 KL
2 carbohydrate metabolic process GO:0005975 9.4 GALNT3 KL
3 phosphatidylinositol-mediated signaling GO:0048015 9.37 FGF23 KL
4 phosphatidylinositol phosphorylation GO:0046854 9.32 FGF23 KL
5 regulation of phosphatidylinositol 3-kinase signaling GO:0014066 9.26 FGF23 KL
6 phosphatidylinositol-3-phosphate biosynthetic process GO:0036092 9.16 FGF23 KL
7 positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway GO:0090080 8.96 FGF23 KL
8 fibroblast growth factor receptor signaling pathway GO:0008543 8.8 FGF23 GALNT3 KL

Molecular functions related to Tumoral Calcinosis, Hyperphosphatemic, Familial according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 Ras guanyl-nucleotide exchange factor activity GO:0005088 9.26 FGF23 KL
2 phosphatidylinositol-4,5-bisphosphate 3-kinase activity GO:0046934 9.16 FGF23 KL
3 1-phosphatidylinositol-3-kinase activity GO:0016303 8.96 FGF23 KL
4 fibroblast growth factor receptor binding GO:0005104 8.62 FGF23 KL

Sources for Tumoral Calcinosis, Hyperphosphatemic, Familial

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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