Taxonomy of rare genetic metabolic bone disorders

Masi, Laura; Agnusdei, D.; Bilezikian, John P.; Chappard, Daniel; Chapurlat, Roland; Cianferotti, Luisella; Devolgelaer, JP; Maghraoui, A. El; Ferrari, Serge; Javaid, M K; Kaufman, Jean M.; Ua, Liberman; Lyritis, George P.; Miller, Paul D.; Napoli, Nicola; Roldán, Emilio J. A.; Papapoulos, Socrates E.; Watts, N B; Brandi, Maria Luisa

doi:10.1007/s00198-015-3188-9

Cited by 34 publications

(35 citation statements)

References 69 publications

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“…Some forms of osteogenesis imperfecta, osteopetrosis, fibrous dysplasia, and o s t e o s c l e r o s i s m a y a l s o p r e s e n t w i t h hyperphosphatasemia. Additional rare conditions include Mabry syndrome, hyperphosphatasia with mental retardation syndrome, familial expansile osteolysis, hyperostosis corticalis generalisata (Van Buchem disease), and Camurati-Engelmann disease [97,100].…”

Section: Hyperphosphatasemiamentioning

confidence: 98%

“…A persistently elevated alkaline phosphatase is seen in a variety of skeletal disease with wide-ranging clinical presentations including various forms of rickets, Paget's disease, and tumoral calcinosis [97]. Some forms of osteogenesis imperfecta, osteopetrosis, fibrous dysplasia, and o s t e o s c l e r o s i s m a y a l s o p r e s e n t w i t h hyperphosphatasemia.…”

Section: Hyperphosphatasemiamentioning

confidence: 99%

“…Dysosteosclerosis, a form of osteopetrosis with a gene mutation localized to SLC29A3, is characterized by short stature, fractures, cranial nerve palsy, delayed developmental milestones, and failure of tooth eruption [96]. Cleidocranial dysplasia, due to a RUNX2 mutation, is associated with abnormal clavicles, short ribs, patent sutures and fontanelles, supernumerary teeth, short stature, and brachydactyly [97]. Mseleni joint disease is a bilateral endemic osteoarthritis that most severely affects the hips in South Africa.…”

Section: Bone Disorders With Abnormal Alkaline Phosphatase Activitymentioning

confidence: 99%

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Hypophosphatasia: Review of Bone Mineral Metabolism, Pathophysiology, Clinical Presentation, Diagnosis, and Treatment

Meah

Basit

Emanuele

et al. 2016

Clinic Rev Bone Miner Metab

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Hypophosphatasia (HPP) is a rare, inherited form of rickets or osteomalacia due to reduced activity of tissue non-specific alkaline phosphatase (TNSALP) caused by a loss of function mutation in the TNSALP gene marked by a low serum alkaline phosphatase. The ratio of PPi to Pi is crucial in the mineralization process. This process is regulated by the interaction of three phosphatases present in matrix vesicles: the mineralization promotors TNSALP and phosphatase orphan 1 (PHOSPHO1) and the mineralization inhibitor nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1). HPP is seen worldwide affecting all races. The broad-ranging clinical severity of HPP is correlated to the pattern of inheritance and degree of TNSALP activity, with lower levels of activity seen in the more severe autosomal recessive forms. HPP is marked by compromise of phase 2 hydroxyapatite crystal formation beyond the matrix vesicle resulting in skeletal hypomineralization, spontaneous fractures, tooth loss, and chondrocalcinosis. The major forms in declining order of severity include the following: perinatal, infantile, childhood, and adult HPP in addition to OdontoHPP and benign prenatal HPP. Biochemistry typically reveals a low serum alkaline phosphatase and elevated alkaline substrates such as pyridoxal-5′-phosphate (PLP) and phosphoethanolamine (PEA). Asfotase alfa, a recent novel enzyme replacement therapy for the treatment of HPP, has transformed this once lethal disease to one that is less severe.

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Section: Hyperphosphatasemiamentioning

confidence: 98%

Section: Hyperphosphatasemiamentioning

confidence: 99%

Section: Bone Disorders With Abnormal Alkaline Phosphatase Activitymentioning

confidence: 99%

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Hypophosphatasia: Review of Bone Mineral Metabolism, Pathophysiology, Clinical Presentation, Diagnosis, and Treatment

Meah

Basit

Emanuele

et al. 2016

Clinic Rev Bone Miner Metab

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“…The study of monogenic diseases with high impact on bone strength has enabled the identification of several pivotal mechanisms involved in bone physiology (22). For example, osteogenesis imperfecta has shown the importance of bone collagen matrix quality; Van Buchem disease, Hajdu-Cheney syndrome and autosomal recessive osteopetrosis have revealed important signalling pathways (namely Wnt, Notch and RANK-RANKL-OPG) that regulate bone remodelling; and pycnodysostosis has given insight into the pivotal action of cathepsin K in osteoclast function.…”

Section: Candidate Genes Emerging From Rare Monogenic Disordersmentioning

confidence: 99%

“…For example, osteogenesis imperfecta has shown the importance of bone collagen matrix quality; Van Buchem disease, Hajdu-Cheney syndrome and autosomal recessive osteopetrosis have revealed important signalling pathways (namely Wnt, Notch and RANK-RANKL-OPG) that regulate bone remodelling; and pycnodysostosis has given insight into the pivotal action of cathepsin K in osteoclast function. On par with a recently proposed taxonomy of rare genetic disorders of bone metabolism (22), monogenic diseases will be presented according to how they affect bone strength. Candidate genes for bone fragility arising from these disorders are presented in Table 1.…”

Section: Candidate Genes Emerging From Rare Monogenic Disordersmentioning

confidence: 99%

Genetics of osteoporosis: searching for candidate genes for bone fragility

Rocha-Braz

Ferraz-de-Souza

2016

Arch. Endocrinol. Metab.

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The pathogenesis of osteoporosis, a common disease with great morbidity and mortality, comprises environmental and genetic factors. As with other complex disorders, the genetic basis of osteoporosis has been difficult to identify. Nevertheless, several approaches have been undertaken in the past decades in order to identify candidate genes for bone fragility, including the study of rare monogenic syndromes with striking bone phenotypes (e.g. osteogenesis imperfecta and osteopetroses), the analysis of individuals or families with extreme osteoporotic phenotypes (e.g. idiopathic juvenile and pregnancy-related osteoporosis), and, chiefly, genome-wide association studies (GWAS) in large populations. Altogether, these efforts have greatly increased the understanding of molecular mechanisms behind bone remodelling, which has rapidly translated into the development of novel therapeutic strategies, exemplified by the tales of cathepsin K (CTSK) and sclerostin (SOST). Additional biological evidence of involvement in bone physiology still lacks for several candidate genes arisen from GWAS, opening an opportunity for the discovery of new mechanisms regulating bone strength, particularly with the advent of high-throughput genomic technologies. In this review, candidate genes for bone fragility will be presented in comprehensive tables and discussed with regard to how their association with osteoporosis emerged, highlighting key players such as LRP5, WNT1 and PLS3. Current limitations in our understanding of the genetic contribution to osteoporosis, such as yet unidentified genetic modifiers, may be overcome in the near future with better genotypic and phenotypic characterisation of large populations and the detailed study of candidate genes in informative individuals with marked phenotype. Arch Endocrinol Metab. 2016;60(4):391-401

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The molecular structure and function of sorting nexin 10 in skeletal disorders, cancers, and other pathological conditions

Qiu

Zhao

et al. 2020

Journal Cellular Physiology

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SNX10 is a member of the phox homology domain-containing family of phosphoinositidebinding proteins. Intracellularly, SNX10 localizes to endosomes where it mediates intracellular trafficking, endosome organization, and protein localization to the centrosome and cilium. It is highly expressed in bone and the gut where it participates in bone mineral and calcium homeostasis through the regulation of osteoclastic bone resorption and gastric acid secretion, respectively. Not surprisingly, patients harboring mutations in SNX10 mutation manifest a phenotype of autosomal recessive osteopetrosis or malignant infantile osteopetrosis, which is clinically characterized by dense bones with increased cortical bone into the medullary space with bone marrow occlusion or depletion, bone marrow failure, and anemia. Accordingly, SNX10 mutant osteoclasts exhibit impaired bone resorptive capacity. Beyond the skeleton, there is emerging evidence implicating SNX10 in cancer development, metabolic disorders, inflammation, and chaperone-mediated autophagy. Understanding the structural basis through which SNX10 exerts its diverse biological functions in both cell and tissue-specific manners may therefore inform new therapeutic opportunities toward the treatment and management of SNX10-related diseases.

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Taxonomy of rare genetic metabolic bone disorders

Cited by 34 publications

References 69 publications

Hypophosphatasia: Review of Bone Mineral Metabolism, Pathophysiology, Clinical Presentation, Diagnosis, and Treatment

Hypophosphatasia: Review of Bone Mineral Metabolism, Pathophysiology, Clinical Presentation, Diagnosis, and Treatment

Genetics of osteoporosis: searching for candidate genes for bone fragility

The molecular structure and function of sorting nexin 10 in skeletal disorders, cancers, and other pathological conditions

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