Dataset Information

Miscellaneous non-inflammatory musculoskeletal conditions. Hyperphosphatemic familial tumoral calcinosis (FGF23, GALNT3 and ?Klotho).

ABSTRACT: Familial tumoral calcinosis (TC) is a rare disorder distinguished by the development of ectopic and vascular calcified masses that occur in settings of hyperphosphatemia (hFTC) and normophosphatemia (nFTC). Serum phosphorus concentrations are relatively tightly controlled by interconnected endocrine activity at the level of the intestine, kidney, and skeleton. Discovering the molecular causes for heritable forms of hFTC has shed new light on the regulation of serum phosphate balance. This review will focus upon the genetic basis and clinical approaches for hFTC, due to genes that are related to the phosphaturic hormone fibroblast growth factor-23 (FGF23). These include FGF23 itself, an FGF23-glycosylating enzyme (GALNT3), and the FGF23 co-receptor ?-Klotho (?KL). Our understanding of the molecular basis of hFTC will, in the short term, aid in understanding normal phosphate balance, and in the future, provide potential insight into the design of novel therapeutic strategies for both rare and common disorders of phosphate metabolism.

SUBMITTER: Farrow EG

PROVIDER: S-EPMC3233725 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Miscellaneous non-inflammatory musculoskeletal conditions. Hyperphosphatemic familial tumoral calcinosis (FGF23, GALNT3 and αKlotho).

Farrow Emily G EG Imel Erik A EA White Kenneth E KE

Best practice & research. Clinical rheumatology 20111001 5

Familial tumoral calcinosis (TC) is a rare disorder distinguished by the development of ectopic and vascular calcified masses that occur in settings of hyperphosphatemia (hFTC) and normophosphatemia (nFTC). Serum phosphorus concentrations are relatively tightly controlled by interconnected endocrine activity at the level of the intestine, kidney, and skeleton. Discovering the molecular causes for heritable forms of hFTC has shed new light on the regulation of serum phosphate balance. This review ...[more]

PMID: 22142751

Similar Datasets

Project description:Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder caused by mutations in FGF23, GALNT3, KLOTHO, or FGF23 autoantibodies. Prominent features include high blood phosphate and calcific masses, usually adjacent to large joints. Dental defects have been reported, but not systematically described. Seventeen patients with HFTC followed at the National Institutes of Health underwent detailed clinical, biochemical, molecular, and dental analyses. Studies of teeth included intraoral photos and radiographs, high-resolution μCT, histology, and scanning electron microscopy (SEM). A scoring system was developed to assess the severity of tooth phenotype. Pulp calcification was found in 13 of 14 evaluable patients. Short roots and midroot bulges with apical thinning were present in 12 of 13 patients. Premolars were most severely affected. μCT analyses of five HFTC teeth revealed that pulp density increased sevenfold, whereas the pulp volume decreased sevenfold in permanent HFTC teeth compared with age- and tooth-matched control teeth. Histology revealed loss of the polarized odontoblast cell layer and an obliterated pulp cavity that was filled with calcified material. The SEM showed altered pulp and cementum structures, without differences in enamel or dentin structures, when compared with control teeth. This study defines the spectrum and confirms the high penetrance of dental features in HFTC. The phenotypes appear to be independent of genetic/molecular etiology, suggesting hyperphosphatemia or FGF23 deficiency may be the pathomechanistic driver, with prominent effects on root and pulp structures, consistent with a role of phosphate and/or FGF23 in tooth development. Given the early appearance and high penetrance, cognizance of HFTC-related features may allow for earlier diagnosis and treatment. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Project description:Hyperphosphatemic familial tumoral calcinosis (HFTC) presents with varied neurological manifestations that have been reported in the literature like facial palsy, vision and hearing impairment, stroke, and headache. In this article, we reported a 12-year-old girl child patient with recurrent facial weakness with bilateral hearing impairment and multiple ulcerative lesions on lower limbs and elbows. On examination, she had lower motor neuron (LMN) facial palsy with conductive hearing loss. The investigations showed hyperphosphatemia (9.3 mg/dL) with normal serum calcium (10.4 mg/dL), alkaline phosphatase (147.9 U/L), parathyroid hormone (23.12 pg/mL), and renal function tests. Elevated serum calcium and phosphorus product (96.72 mg 2 /mL 2 ) and elevated renal tubular reabsorption of phosphate (TMPxGFR) value (9.16) were noted. Skeletal survey showed hyperostosis in the long bone diaphysis, vertebrae, ribs, pelvic bone, skull, and facial bones with narrowing of cranial ostium, characteristically without any peri-articular soft tissue calcifications. An angiogram showed multiple intravascular calcifications. She was managed with a low-phosphate diet, sevelamer, niacinamide, acetazolamide, sucroferric oxyhydroxide to lower serum phosphate level, and topical sodium thiosulfate ectopic cutaneous calcification. Exome sequencing showed novel homozygous inframe deletion of ACG in FGF23 gene exon 3 at c.374_376 delins position (p. Asp125del) in the proband and a mutation in the heterozygous state in the mother and elder sibling, thus confirming a molecular diagnosis of HFTC. Our case had a unique neurological presentation of recurrent bilateral lower motor nerve facial palsy, hearing loss, multiple ectopic cutaneous calcifications without peri-articular deposits, multiple intravascular, intracranial, and vertebral endplate calcification, which has not been reported earlier. The proband showed a novel pathogenic variant suggesting an expanding phenotype of HFTC.

Dataset Information

Miscellaneous non-inflammatory musculoskeletal conditions. Hyperphosphatemic familial tumoral calcinosis (FGF23, GALNT3 and ?Klotho).

Publications

Miscellaneous non-inflammatory musculoskeletal conditions. Hyperphosphatemic familial tumoral calcinosis (FGF23, GALNT3 and αKlotho).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets