Enthesopathy as the presenting feature of X-linked hypophosphatemia: A case report

Chalmers, John

doi:10.3109/17453679308994575

Cited by 7 publications

(3 citation statements)

References 5 publications

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“…One important factor suggested by our study, and the literature, is FGF23. Increased circulating FGF23 and hypophosphatemia occurs in patients with calcifying enthesopathies in rare metabolic disorders such as ARHR2 and XLH (9,(42)(43)(44)(45)(46)(47) and in the general medical population in patients with rapidly progressive forms of OPLL. (48,49) In contrast, calcifying enthesopathies are not associated with FGF23-independent forms of hypophosphatemic rickets, such as SLC34A3 deficiency.…”

Section: Discussionmentioning

confidence: 99%

Identification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early-Onset Osteoporosis

Katô

Ansh

Lester

et al. 2020

Journal of Bone and Mineral Research

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Homozygous ENPP1 mutations are associated with autosomal recessive hypophosphatemic rickets type 2 (ARHR2), severe ossification of the spinal ligaments, and generalized arterial calcification of infancy type 1. There are a limited number of reports on phenotypes associated with heterozygous ENPP1 mutations. Here, we report a series of three probands and their families with heterozygous and compound heterozygous ENPP1 mutations. The first case (case 1) was a 47-year-old male, diagnosed with early-onset osteoporosis and low-normal serum phosphate levels, which invoked suspicion for hypophosphatemic rickets. The second and third cases were 77-and 54-year-old females who both presented with severe spinal ligament ossification and the presumptive diagnosis of diffuse idiopathic skeletal hyperostosis (DISH). Upon workup, fibroblast growth factor 23 (FGF23) was noted to be relatively high in case 2 and serum phosphorous was low-normal in case 3, and the diagnoses of X-linked hypophosphatemic rickets (XLH) and ARHR2 were considered. Genetic testing for genes related to congenital hypophosphatemic rickets was therefore performed, revealing heterozygous ENPP1 variants in cases 1 and 2 (case 1, c.536A>G, p.Asn179Ser; case 2, c.1352A>G, p.Tyr451Cys) and compound heterozygous ENPP1 variants in case 3 constituting the same variants present in cases 1 and 2 (c.536A>G, p.Asn179Ser and c.1352A>G, p.Tyr451Cys). Several in silico tools predicted the two variants to be pathogeneic, a finding confirmed by in vitro biochemical analysis demonstrating that the p.Asn179Ser and p.Tyr451Cys ENPP1 variants possessed a catalytic velocity of 45% and 30% compared with that of wildtype ENPP1, respectively. Both variants were therefore categorized as pathogenic loss-of-function mutations. Our findings suggest that ENPP1 mutational status should be evaluated in patients presenting with the diagnosis of idiopathic DISH, ossification of the posterior longitudinal ligament (OPLL), and early-onset osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Identification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early-Onset Osteoporosis

Katô

Ansh

Lester

et al. 2020

Journal of Bone and Mineral Research

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“…La patogenesi delle lesioni entesopatiche di OV-DR non è ancora del tutto chiara. La gravità dell'entesopatia nei nostri pazienti non era correlata all'entità delle modificazioni bioumorali, come osservato da altri autori (1,7,8). Riguardo l'effetto iatrogeno del calcitriolo, il farmaco più frequentemente usato per il trattamento di OVDR, Hardy et al ( 4) hanno escluso una relazione tra entesopatia associata a OVDR e terapia.…”

Section: Discussioneunclassified

The enthesopathy of vitamin D-resistant osteomalacia in adults

Ramonda

Sfriso²,

Podswiadek³

et al. 2011

Reumatismo

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A case of an adult patient with vitamin D-resistant osteomalacia or X-linked hypophosphatemic osteomalacia (XLH) with diffuse calcification of entheses was reported. XLH is the most frequent cause of rickets in developed countries. It is characterized by an impaired renal transport of the phosphate and mutation of PFEX (phosphate regulating gene, with homologies to endopeptidase on the X-chromosome). In childhood, the classic clinical presentation includes short stature and bow leg. While at this age the main radiographic features are characterised by rickets, in adult life they are dominated by a generalised calcific enthesopathy. Concerning the pathogenesis of the enthesopathic lesions of XLH, no convincing hypothesis has yet been made. As in our patient, the extension and the severity of enthesopathy seems not related to the severity of the biochemical changes nor to the treatment with calcitriol. The calcified enthesopathy is an integral part of XLH and it is possible that it is found in adult because many years are necessary to produce it

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“…Both enthesopathy and osteoarthritis in XLH and ARHR increase with age and cause severe pain, stiffness, and difficulty performing tasks of everyday life. Enthesis-related complications are therefore of considerable clinical importance and represent significant morbidity in these patients (67)(68)(69)(70)(71)(72)(73). These occur frequently, particularly at the knees, ankles, pelvis, and thoracic/cervical spine sites, typically increasing with age (70).…”

Section: Enthesis and Enthesopathiesmentioning

confidence: 99%

ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency

Ferreira,

Carpenter,

Braddock

2024

Annu. Rev. Pathol. Mech. Dis.

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The enzyme ectonucleotide pyrophosphatase/phosphodiesterase-1 ( ENPP1) codes for a type 2 transmembrane glycoprotein that hydrolyzes extracellular ATP to generate pyrophosphate (PPi) and adenosine monophosphate, thereby contributing to downstream purinergic signaling pathways. The clinical phenotypes induced by ENPP1 deficiency are seemingly contradictory and include early-onset osteoporosis in middle-aged adults and life-threatening vascular calcifications in the large arteries of infants with generalized arterial calcification of infancy. The progressive overmineralization of soft tissue and concurrent undermineralization of skeleton also occurs in the general medical population, where it is referred to as paradoxical mineralization to highlight the confusing pathophysiology. This review summarizes the clinical presentation and pathophysiology of paradoxical mineralization unveiled by ENPP1 deficiency and the bench-to-bedside development of a novel ENPP1 biologics designed to treat mineralization disorders in the rare disease and general medical population. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 19 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Enthesopathy as the presenting feature of X-linked hypophosphatemia: A case report

Cited by 7 publications

References 5 publications

Identification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early-Onset Osteoporosis

Identification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early-Onset Osteoporosis

The enthesopathy of vitamin D-resistant osteomalacia in adults

ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency

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