更新于：2024-11-01

Tumoral Calcinosis, Hyperphosphatemic, Familial

高磷酸盐家族性肿瘤钙质沉着症

更新于：2024-11-01

基本信息

别名

CALCINOSIS, TUMORAL, WITH HYPERPHOSPHATEMIA、CORTICAL HYPEROSTOSIS WITH HYPERPHOSPHATEMIA、Calcinosis, Tumoral, With Hyperphosphatemia

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简介

An autosomal recessive disorder caused by loss-of-function mutation(s) in the GALNT3, FGF23, or KL gene, which encode polypeptide N-acetylgalactosaminyltransferase 3, fibroblast growth factor 23, and klotho, respectively. This condition, the biochemical hallmark of which is hyperphosphatemia caused by increased renal phosphate absorption, is characterized by the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and/or bone.

关联

项与高磷酸盐家族性肿瘤钙质沉着症相关的药物

Bixalomer

比沙洛姆

靶点

Phosphates

作用机制

Phosphates 调节剂

在研机构

Astellas Pharma, Inc.

原研机构

Ilypsa, Inc.

在研适应症

高磷血症

非在研适应症

慢性肾病 [+3]

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期2012-03-30

项与高磷酸盐家族性肿瘤钙质沉着症相关的临床试验

NCT00530114 / Completed临床2期

A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel Group, Fixed Dose Study of AMG 223 in Subjects With Chronic Kidney Disease on Hemodialysis With Hyperphosphatemia

The primary objectives of this study are the following:
To demonstrate that AMG 223 will produce a statistically significant reduction in serum phosphorus compared with placebo over a 3 week treatment period in subjects with CKD receiving dialysis
To describe a dose response for AMG 223
To evaluate the safety and tolerability of AMG 223

开始日期2008-03-01

申办/合作机构

Amgen, Inc.

NCT00024804 / RecruitingN/AIIT

A Natural History Study of Bone and Mineral Disorders

This study has four objectives: 1) to provide investigators the opportunity to study bone specimens from patients with various skeletal diseases; 2) to treat patients with skeletal diseases at the NIH; 3) to expose NIH trainees to certain skeletal diseases; and 4) to gain more knowledge about skeletal diseases and stimulate further study of bone biology.
Anyone with a disease that affects the skeleton may be eligible for this study.
All evaluations, tests, procedures and treatments given study participants are used in the standard care of skeletal diseases. No experimental evaluations or treatments are offered. Patient evaluations include a medical history, review of medical records and routine physical examination. Based on the findings, other procedures may be recommended, including blood tests, urine tests, and imaging tests, such as X-rays, bone densitometry, bone scan, computed tomography (CT) and magnetic resonance imaging (MRI).
Bone specimens from participants will be collected for research use. Specimens will be obtained from bone removed during a patient s planned surgical procedure performed for medical care, or patients may be requested to have a bone biopsy removal of a small piece of bone tissue as part of the patient evaluation procedure.

开始日期2001-11-19

申办/合作机构

National Institute of Dental & Craniofacial Research

100 项与高磷酸盐家族性肿瘤钙质沉着症相关的临床结果

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100 项与高磷酸盐家族性肿瘤钙质沉着症相关的转化医学

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0 项与高磷酸盐家族性肿瘤钙质沉着症相关的专利（医药）

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137

项与高磷酸盐家族性肿瘤钙质沉着症相关的文献（医药）

2024-09-02·Journal of Bone and Mineral Research

Structural and molecular imaging-based characterization of soft tissue and vascular calcification in hyperphosphatemic familial tumoral calcinosis

Article

作者: Roszko, Kelly L ; Collins, Michael T ; Saboury, Babak ; Farhadi, Faraz ; Paravastu, Sriram S ; Donnelly, Eve ; Sheppard, Aaron J ; Gafni, Rachel I ; Hartley, Iris R

AbstractHyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disorder caused by deficient FGF23 signaling and resultant ectopic calcification. Here, we systematically characterized and quantified macro- and micro-calcification in a HFTC cohort using CT and 18F-sodium fluoride PET/CT (18F-NaF PET/CT). Fourier-transform infrared (FTIR) spectroscopy was performed on 4 phenotypically different calcifications from a patient with HFTC, showing the dominant component to be hydroxyapatite. Eleven patients with HFTC were studied with CT and/or 18F-NaF PET/CT. Qualitative review was done to describe the spectrum of imaging findings on both modalities. CT-based measures of volume (eg, total calcific burden and lesion volume) and density (Hounsfield units) were quantified and compared to PET-based measures of mineralization activity (eg, mean standardized uptake values—SUVs). Microcalcification scores were calculated for the vasculature of 6 patients using 18F-NaF PET/CT and visualized on a standardized vascular atlas. Ectopic calcifications were present in 82% of patients, predominantly near joints and the distal extremities. Considerable heterogeneity was observed in total calcific burden per patient (823.0 ± 670.1 cm3, n = 9) and lesion volume (282.5 ± 414.8 cm3, n = 27). The largest lesions were found at the hips and shoulders. 18F-NaF PET offered the ability to differentiate active vs quiescent calcifications. Calcifications were also noted in multiple anatomic locations, including brain parenchyma (50%). Vascular calcification was seen in the abdominal aorta, carotid, and coronaries in 50%, 73%, and 50%, respectively. 18F-NaF-avid, but CT-negative calcification was seen in a 17-year-old patient, implicating early onset vascular calcification. This first systematic assessment of calcifications in a cohort of patients with HFTC has identified the early onset, prevalence, and extent of calcification. It supports 18F-NaF PET/CT as a clinical tool for distinguishing between active and inactive calcification, informing disease progression, and quantification of ectopic and vascular disease burden.

2024-09-01·Molecular Genetics and Metabolism Reports

A GALNT3 mutation causing Hyperphosphatemic familial Tumoral calcinosis

Article

作者: Yang, Bangxiang ; Yu, Xijie ; Wu, Aijia

Aim Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) is an autosomal recessive disorder. This study investigates the etiology of HFTC in offspring from consanguineous parents.MethodsClinical assessment, imaging, and direct sequencing were utilized to elucidate the condition. Previously reported cases were also reviewed.ResultWe identified a consanguineous Chinese family with HFTC caused by an interesting homozygous G to A substitution in GALNT3 (c.1626 + 1G > A). The parents were carriers.ConclusionThis study represents the first report of HFTC in a consanguineous Chinese family due to an interesting GALNT3 mutation. We reviewed known GALNT3 variants and associated clinical features of calcification disorders. The phenotypic difference between homozygous and complex heterozygous mutations is not clinically significant. Gene mutations affect the function of proteins mainly by affecting their binding to polyvalent ligands.

2024-09-01·Journal of Biological Chemistry

In vivo mapping of the mouse Galnt3-specific O-glycoproteome

Article

作者: Ten Hagen, Kelly G ; Yang, Weiming ; Dalal, Kruti ; Tian, E ; Tabak, Lawrence A ; Lara, Alexander J ; Chernish, Aliona ; McCluggage, Peggy

The UDP-N-acetylgalactosamine polypeptide:N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes initiates O-linked glycosylation by catalyzing the addition of the first GalNAc sugar to serine or threonine on proteins destined to be membrane-bound or secreted. Defects in individual isoforms of the GalNAc-T family can lead to certain congenital disorders of glycosylation (CDG). The polypeptide N-acetylgalactosaminyltransferase 3 (GALNT)3-CDG, is caused by mutations in GALNT3, resulting in hyperphosphatemic familial tumoral calcinosis due to impaired glycosylation of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) within osteocytes of the bone. Patients with hyperphosphatemia present altered bone density, abnormal tooth structure, and calcified masses throughout the body. It is therefore important to identify all potential substrates of GalNAc-T3 throughout the body to understand the complex disease phenotypes. Here, we compared the Galnt3^-/- mouse model, which partially phenocopies GALNT3-CDG, with WT mice and used a multicomponent approach using chemoenzymatic conditions, a product-dependent method constructed using EThcD triggered scans in a mass spectrometry workflow, quantitative O-glycoproteomics, and global proteomics to identify 663 Galnt3-specific O-glycosites from 269 glycoproteins across multiple tissues. Consistent with the mouse and human phenotypes, functional networks of glycoproteins that contain GalNAc-T3-specific O-glycosites involved in skeletal morphology, mineral level maintenance, and hemostasis were identified. This library of in vivo GalNAc-T3-specific substrate proteins and O-glycosites will serve as a valuable resource to understand the functional implications of O-glycosylation and to unravel the underlying causes of complex human GALNT3-CDG phenotypes.