Pseudoxanthoma elasticum in hyperphosphatasia

Df, Fretzin

doi:10.1001/archderm.111.2.271

Cited by 6 publications

(6 citation statements)

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“…Our patient had small head size, rather than the macrocranium typical of JPD. (3)(4)(5)(6)(7)(8)(9)(10)(11) Although she lived in a tropical area of southern Iran, her sunlight exposure was probably limited by her disabilities that kept her indoors in a city. Furthermore, she was breastfed during infancy without receiving supplemental vitamin D. Her mother's exposure to sunlight was likely also limited because she wore the burka customary for women in this part of Iran.…”

Section: Discussionmentioning

confidence: 99%

“…4). At 2.5 years-of-age, her findings were again typical for JPD (3)(4)(5)(6)(7)(8)(9)(10)(11) and included widened osteopenic long bones with coarse trabeculae and indistinct Fig. 2.…”

Section: Radiographic Findingsmentioning

confidence: 96%

“…(3) Approximately 60 cases have been reported worldwide. (3)(4)(5)(6)(7)(8)(9)(10)(11) Affected infants and children suffer bone pain, fractures, and skeletal deformities and most become deaf by early childhood. (4,6,7) Those who live longer may acquire diffuse vascular microcalcification (VMC) (8) that causes retinopathy and blindness (5,10) and perhaps intracranial aneurysms.…”

Section: Introductionmentioning

confidence: 99%

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Juvenile Paget's disease in an Iranian kindred with vitamin D deficiency and novel homozygous TNFRSF11B mutation

Saki

Karamizadeh

Nasirabadi

et al. 2013

Journal of Bone and Mineral Research

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Juvenile Paget’s disease (JPD) is a rare heritable osteopathy characterized biochemically by markedly increased serum alkaline phosphatase (ALP) activity emanating from generalized acceleration of skeletal turnover. Affected infants and children typically suffer bone pain and fractures and deformities, become deaf, and have macrocranium. Some who survive to young adult life develop blindness from retinopathy engendered by vascular microcalcification. Most cases of JPD are caused by osteoprotegerin (OPG) deficiency due to homozygous loss-of-function mutations within the TNFRSF11B gene that encodes OPG. We report a 3-year-old Iranian girl with JPD and craniosynostosis who had vitamin D deficiency in infancy. She presented with fractures during the first year-of-life followed by bone deformities, delayed development, failure-to-thrive, and pneumonias. At 1 year-of-age, biochemical studies of serum revealed marked hyperphosphatasemia together with low-normal calcium and low inorganic phosphate and 25-hydroxyvitamin D levels. Several family members in previous generations of this consanguineous kindred may also have had JPD and vitamin D deficiency. Mutation analysis showed homozygosity for a unique missense change (c.130T>C, p.Cys44Arg) in TNFRSF11B that would compromise the cysteine-rich domain of OPG that binds receptor activator of NF-κB ligand (RANKL). Both parents were heterozygous for this mutation. The patient’s serum OPG level was extremely low and RANKL level markedly elevated. She responded well to rapid oral vitamin D repletion followed by pamidronate treatment given intravenously. Our patient is the first Iranian reported with JPD. Her novel mutation in TNFRSF11B plus vitamin D deficiency in infancy was associated with severe JPD uniquely complicated by craniosynostosis. Pamidronate treatment with vitamin D sufficiency can be effective treatment for the skeletal disease caused by the OPG deficiency form of JPD.

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Section: Discussionmentioning

confidence: 99%

“…4). At 2.5 years-of-age, her findings were again typical for JPD (3)(4)(5)(6)(7)(8)(9)(10)(11) and included widened osteopenic long bones with coarse trabeculae and indistinct Fig. 2.…”

Section: Radiographic Findingsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Juvenile Paget's disease in an Iranian kindred with vitamin D deficiency and novel homozygous TNFRSF11B mutation

Saki

Karamizadeh

Nasirabadi

et al. 2013

Journal of Bone and Mineral Research

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“…(7)(8)(9) If untreated with antiresorptive pharmaceuticals, JPD can be fatal by early adult life. (7,10) Those who survive longer may have features of pseudoxanthoma elasticum, (10,11) including widespread vascular calcification (10) and retinopathy causing blindness. (12) Approximately 50 cases are described in the medical literature.…”

Section: Introductionmentioning

confidence: 99%

Juvenile Paget's Disease: The Second Reported, Oldest Patient Is Homozygous for the TNFRSF11B “Balkan” Mutation (966_969delTGACinsCTT), Which Elevates Circulating Immunoreactive Osteoprotegerin Levels

Whyte

Singhellakis

Petersen

et al. 2007

Journal of Bone and Mineral Research

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The oldest person (60 yr) with juvenile Paget's disease is homozygous for the TNFRSF11B mutation 966_969delTGACinsCTT. Elevated circulating levels of immunoreactive OPG and soluble RANKL accompany this genetic defect that truncates the OPG monomer, preventing formation of OPG homodimers.Introduction: Juvenile Paget's disease (JPD), a rare autosomal recessive disorder, features skeletal pain, fracture, and deformity from extremely rapid bone turnover. Deafness and sometimes retinopathy also occur. Most patients have diminished osteoprotegerin (OPG) inhibition of osteoclastogenesis caused by homozygous loss-of-function defects in TNFRSF11B, the gene that encodes OPG. Circulating immunoreactive OPG (iOPG) is undetectable with complete deletion of TNFRSF11B but normal with a 3-bp in-frame deletion. Materials and Methods:We summarize the clinical course of a 60-yr-old Greek man who is the second reported, oldest JPD patient, including his response to two decades of bisphosphonate therapy. Mutation analysis involved sequencing all exons and adjacent mRNA splice sites of TNFRSF11B. Over the past 4 yr, we used ELISAs to quantitate his serum iOPG and soluble RANKL (sRANKL) levels. Results: Our patient suffered progressive deafness and became legally blind, although elevated markers of bone turnover have been normal for 6 yr. He carries the same homozygous mutation in TNFRSF11B (966_969delTGACinsCTT) reported in a seemingly unrelated Greek boy and Croatian man who also have relatively mild JPD. This frame-shift deletes 79 carboxyterminal amino acids from the OPG monomer, including a cysteine residue necessary for homodimerization. Nevertheless, serum iOPG and sRANKL levels are persistently elevated. Conclusions: Homozygosity for the TNFRSF11B "Balkan" mutation (966_969delTGACinsCTT) causes JPD in the second reported, oldest patient. Elevated circulating iOPG and sRANKL levels complement evidence that this deletion/insertion omits a cysteine residue at the carboxyterminus needed for OPG homodimerization.

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“…(5)(6)(7) Until bone antiresorptive pharmaceuticals became available, JPD was often fatal by young adult life. (5,8) If survival was longer, generalized arterial calcification resembling this complication in pseudoxanthoma elasticum (8,9) frequently led to retinopathy with blindness, (10) and perhaps also explained rare cerebral artery aneurysms. (11) Some patients with a variant of JPD had relatively mild skeletal disease but with significant mental retardation.…”

Section: Ii) Introductionmentioning

confidence: 99%

Juvenile Paget's Disease From Heterozygous Mutation of SP7 Encoding Osterix (Specificity Protein 7, Transcription Factor SP7)

Whyte

Campeau

McAlister

et al. 2020

Bone

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Pseudoxanthoma elasticum in hyperphosphatasia

Cited by 6 publications

References 0 publications

Juvenile Paget's disease in an Iranian kindred with vitamin D deficiency and novel homozygous TNFRSF11B mutation

Juvenile Paget's disease in an Iranian kindred with vitamin D deficiency and novel homozygous TNFRSF11B mutation

Juvenile Paget's Disease: The Second Reported, Oldest Patient Is Homozygous for the TNFRSF11B “Balkan” Mutation (966_969delTGACinsCTT), Which Elevates Circulating Immunoreactive Osteoprotegerin Levels

Juvenile Paget's Disease From Heterozygous Mutation of SP7 Encoding Osterix (Specificity Protein 7, Transcription Factor SP7)

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