MCID: TMR011
MIFTS: 50

Tumoral Calcinosis, Hyperphosphatemic, Familial

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

Aliases & Classifications for Tumoral Calcinosis, Hyperphosphatemic, Familial

MalaCards integrated aliases for Tumoral Calcinosis, Hyperphosphatemic, Familial:

Name: Tumoral Calcinosis, Hyperphosphatemic, Familial 53 49 71 69
Hftc 53 12 23 49 24 71
Hyperostosis-Hyperphosphatemia Syndrome 53 23 49 71 69
Hyperphosphatemic Familial Tumoral Calcinosis 12 23 49 24
Cortical Hyperostosis with Hyperphosphatemia 53 12 49 71
Hyperostosis with Hyperphosphatemia 53 12 49 71
Hhs 53 12 49 71
Primary Hyperphosphatemic Tumoral Calcinosis 12 23 24
Tumoral Calcinosis, Hyperphosphatemic 53 13 51
Lipocalcinogranulomatosis 53 12 71
Morbus Teutschlaender 53 12 71
Phptc 53 12 71
Familial Hyperphosphatemic Tumoral Calcinosis/hyperphosphatemic Hyperostosis Syndrome 12 55
Hyperphosphatemia Hyperostosis Syndrome 12 24
Hyperphosphatemia Tumoral Calcinosis 12 24
Hypercalcemic Tumoral Calcinosis 12 55
Hyperphosphatemia Hyperostosis 12 24
Familial Tumoral Calcinosis/hyperostosis-Hyperphosphatemia Syndrome 23
Tumoral Calcinosis, Primary Hyperphosphatemic; Phptc 53
Familial Tumoral Calcinosis with Hyperphosphatemia 71
Tumoral Calcinosis, Familial, Hyperphosphatemic 28
Tumoral Calcinosis, Primary Hyperphosphatemic 53
Hyperostosis-Hyperphosphatemia Syndrome; Hhs 53
Tumoral Calcinosis Primary Hyperphosphatemic 71
Calcinosis, Tumoral, with Hyperphosphatemia 53
Tumoral Calcinosis with Hyperphosphatemia 12
Teutschlaender Disease, Familial 53
Familial Teutschlaender Disease 12
Teutschlaender Disease 71
Tumoral Calcinosis 69
Ftc/hhs 23

Characteristics:

Orphanet epidemiological data:

55

OMIM:

53
Inheritance:
autosomal recessive

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


HPO:

31
tumoral calcinosis, hyperphosphatemic, familial:
Onset and clinical course juvenile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Tumoral Calcinosis, Hyperphosphatemic, Familial

OMIM : 53 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 hyperphosphatemia and hyperostosis, and has symptoms including nephrocalcinosis, taurodontia and abnormality of the skin. An important gene associated with Tumoral Calcinosis, Hyperphosphatemic, Familial is FGF23 (Fibroblast Growth Factor 23), and among its related pathways/superpathways are Negative regulation of FGFR3 signaling and O-linked glycosylation. 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 limbs/digits/tail and renal/urinary system

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 : 24 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.

Wikipedia : 72 Tumoral calcinosis is a rare condition in which there is calcium deposition in the soft tissue in... more...

GeneReviews: NBK476672

Related Diseases for Tumoral Calcinosis, Hyperphosphatemic, Familial

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

(show all 49)
# Related Disease Score Top Affiliating Genes
1 hyperphosphatemia 29.5 FGF23 GALNT3 KL
2 hyperostosis 29.4 FGF23 GALNT3 KL
3 calcinosis 28.8 FGF23 GALNT3 KL
4 familial tumoral calcinosis 28.5 FGF23 GALNT3 KL POMGNT2
5 hypotrichosis 1 11.7
6 hemochromatosis, type 1 11.5
7 dyskeratosis congenita, x-linked 11.5
8 hypogonadotropic hypogonadism 7 with or without anosmia 11.4
9 heart-hand syndrome, slovenian type 11.4
10 hypothalamic hamartomas 11.0
11 charge syndrome 11.0
12 dyskeratosis congenita, autosomal dominant 1 10.9
13 hypogonadotropic hypogonadism 2 with or without anosmia 10.9
14 dyskeratosis congenita, autosomal recessive 5 10.9
15 kallmann syndrome 10.9
16 hyperinsulinemic hypoglycemia, familial, 6 10.9
17 hypotrichosis simplex 10.9
18 hypogonadotropic hypogonadism 3 with or without anosmia 10.7
19 hypogonadotropic hypogonadism 4 with or without anosmia 10.7
20 hypogonadotropic hypogonadism 5 with or without anosmia 10.7
21 hypogonadotropic hypogonadism 6 with or without anosmia 10.7
22 hypogonadotropic hypogonadism 8 with or without anosmia 10.7
23 hypogonadotropic hypogonadism 9 with or without anosmia 10.7
24 hypogonadotropic hypogonadism 10 with or without anosmia 10.7
25 hypogonadotropic hypogonadism 11 with or without anosmia 10.7
26 hypogonadotropic hypogonadism 12 with or without anosmia 10.7
27 hypogonadotropic hypogonadism 13 with or without anosmia 10.7
28 hypogonadotropic hypogonadism 14 with or without anosmia 10.7
29 hypogonadotropic hypogonadism 15 with or without anosmia 10.7
30 hypogonadotropic hypogonadism 16 with or without anosmia 10.7
31 hypogonadotropic hypogonadism 17 with or without anosmia 10.7
32 hypogonadotropic hypogonadism 18 with or without anosmia 10.7
33 hypogonadotropic hypogonadism 19 with or without anosmia 10.7
34 hypogonadotropic hypogonadism 20 with or without anosmia 10.7
35 hypogonadotropic hypogonadism 21 with or without anosmia 10.7
36 hypogonadotropic hypogonadism 22 with or without anosmia 10.7
37 hypogonadotropic hypogonadism 9.9
38 hypogonadism 9.9
39 tracheal calcification 9.9 FGF23 KL
40 hypophosphatemic rickets, x-linked dominant 9.8 FGF23 KL
41 hypophosphatemic rickets, autosomal dominant 9.7 FGF23 GALNT3
42 urinary system disease 9.7 FGF23 KL
43 arterial calcification of infancy 9.6 FGF23 GALNT3
44 lacrimoauriculodentodigital syndrome 9.6 FGF23 GALNT3
45 autosomal dominant polycystic kidney disease 9.5 FGF23 KL
46 hypervitaminosis d 9.3 FGF23 GALNT3 KL
47 phosphorus metabolism disease 9.3 FGF23 GALNT3 KL
48 hypophosphatemic rickets with hypercalciuria, hereditary 9.3 FGF23 GALNT3 KL
49 mineral metabolism disease 9.3 FGF23 GALNT3 KL

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:

53
HeadAndNeckTeeth:
pulp stones
taurodontism
thin dental enamel
obliterated tooth pulp cavities
disturbed root development
more
SkeletalLimbs:
cortical hyperostosis
painful swellings of the long bones, acute, recurrent attacks
periosteal reaction
diaphysitis
radiography shows porotic changes
more
CardiovascularVascular:
vascular calcifications

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

LaboratoryAbnormalities:
hyperphosphatemia
normal serum calcium
normal serum parathyroid hormone (pth)
normal to elevated serum 1,25-dihydroxycholecalciferol (calcitriol)
increased serum fgf23
more
HeadAndNeckEyes:
angioid streaks, retina
conjunctival irritation
conjunctival whitish 'salt-like' deposits

GenitourinaryKidneys:
increased renal tubular phosphate reabsorption
decreased renal tubular phosphate excretion
calcinosis of the renal parenchyma

SkinNailsHairSkin:
deposition of calcium phosphate crystals in skin and subcutaneous tissues


Clinical features from OMIM:

211900

Human phenotypes related to Tumoral Calcinosis, Hyperphosphatemic, Familial:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 nephrocalcinosis 31 HP:0000121
2 taurodontia 31 HP:0000679
3 abnormality of the skin 31 HP:0000951
4 pulp stones 31 HP:0003771
5 hypoplasia of dental enamel 31 HP:0006297
6 hyperphosphatemia 31 HP:0002905
7 calcinosis 31 HP:0003761
8 increased renal tubular phosphate reabsorption 31 HP:0005571
9 decreased renal tubular phosphate excretion 31 HP:0005572
10 angioid streaks of the fundus 31 HP:0001102
11 vascular calcification 31 HP:0004934
12 conjunctival whitish salt-like deposits 31 HP:0007799

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

43
# Description MGI Source Accession Score Top Affiliating Genes
1 limbs/digits/tail MP:0005371 9.13 FGF23 GALNT3 KL
2 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)
# 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 Micronutrients
4 Chelating Agents
5 Trace Elements
6 Vitamins
7 Hydroxycholecalciferols
8 Bone Density Conservation Agents

Interventional clinical trials:


# 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:

# Genetic test Affiliating Genes
1 Tumoral Calcinosis, Familial, Hyperphosphatemic 28

Anatomical Context for Tumoral Calcinosis, Hyperphosphatemic, Familial

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

38
Skin, Bone, Brain, Retina

Publications for Tumoral Calcinosis, Hyperphosphatemic, Familial

Articles related to Tumoral Calcinosis, Hyperphosphatemic, Familial:

# Title Authors Year
1
Phenotypic and Genotypic Characterization and Treatment of a Cohort with Familial Tumoral Calcinosis/Hyperostosis-Hyperphosphatemia Syndrome. ( 27164190 )
2016
2
Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC). ( 26337219 )
2015
3
Hyperostosis-hyperphosphatemia syndrome (HHS): report of two cases with a recurrent mutation and review of the literature. ( 25153226 )
2014
4
A new missense mutation in FGF23 gene in a male with hyperostosis-hyperphosphatemia syndrome (HHS). ( 24680727 )
2014
5
Newly discovered mutations in the GALNT3 gene causing autosomal recessive hyperostosis-hyperphosphatemia syndrome. ( 19297793 )
2009
6
A case of familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome due to a compound heterozygous mutation in GALNT3 demonstrating new phenotypic features. ( 18982401 )
2009
7
Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact fibroblast growth factor 23 concentrations. ( 17311862 )
2007
8
Hyperostosis-hyperphosphatemia syndrome: a congenital disorder of O-glycosylation associated with augmented processing of fibroblast growth factor 23. ( 17129170 )
2007
9
Identification of a recurrent mutation in GALNT3 demonstrates that hyperostosis-hyperphosphatemia syndrome and familial tumoral calcinosis are allelic disorders. ( 15599692 )
2005

Variations for Tumoral Calcinosis, Hyperphosphatemic, Familial

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

71
# 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 19)
# 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
18 FGF23 NM_020638.2(FGF23): c.385T> C (p.Ser129Pro) single nucleotide variant Pathogenic GRCh38 Chromosome 12, 4370714: 4370714
19 FGF23 NM_020638.2(FGF23): c.367G> T (p.Gly123Trp) single nucleotide variant Pathogenic GRCh38 Chromosome 12, 4370732: 4370732

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:

# Name GO ID Score Top Affiliating Genes
1 carbohydrate metabolic process GO:0005975 9.4 GALNT3 KL
2 protein glycosylation GO:0006486 9.37 GALNT3 POMGNT2
3 positive regulation of protein kinase B signaling GO:0051897 9.32 FGF23 KL
4 phosphatidylinositol phosphorylation GO:0046854 9.26 FGF23 KL
5 phosphatidylinositol-3-phosphate biosynthetic process GO:0036092 9.16 FGF23 KL
6 positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway GO:0090080 8.96 FGF23 KL
7 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:

# Name GO ID Score Top Affiliating Genes
1 transferase activity, transferring glycosyl groups GO:0016757 9.32 GALNT3 POMGNT2
2 Ras guanyl-nucleotide exchange factor activity GO:0005088 9.26 FGF23 KL
3 phosphatidylinositol-4,5-bisphosphate 3-kinase activity GO:0046934 9.16 FGF23 KL
4 1-phosphatidylinositol-3-kinase activity GO:0016303 8.96 FGF23 KL
5 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
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....