Enzyme-Replacement Therapy in Life-Threatening Hypophosphatasia

Whyte, Michael P.; Greenberg, Cheryl R.; Salman, Nada; Bober, Michael B.; McAlister, William H.; Wenkert, Deborah; Sickle, Bradley J. Van; Simmons, Jill H.; Edgar, Terence S.; Bauer, Martin; Hamdan, Mohamed A.; Bishop, Nick; Lutz, Richard E.; McGinn, Mairead; Craig, Stanley; Moore, Jean; Taylor, John W.; Cleveland, Robert H.; Cranley, William R.; Lim, Ruth; Thacher, Tom D.; Mayhew, J.; Downs, Matthew; Millán, José Luis; Skrinar, Alison; Crine, Philippe; Landy, Hal

doi:10.1056/nejmoa1106173

Cited by 472 publications

(424 citation statements)

References 30 publications

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“…(54,55) The radiographic features of pediatric HPP can include severe rachitic disease with widened physes, irregular provisional zones of calcification, lucent defects, and intervening areas of sclerosis within flared metaphyses, focal ''tongues'' of radiolucency that extend into metaphyses from physes, bowed long bones, increased digital markings with a ''beaten copper'' appearance of the skull from premature bony fusion of cranial sutures, and a widened diploic space. (30,53) Enlarged pulp chambers in teeth are sometimes observed. (53) HPP in adults features osteomalacia and sometimes complications of calcium pyrophosphate dihydrate (CPPD) deposition, or calcific periarthritis from seemingly paradoxical formation of HA near joints.…”

Section: Discussionmentioning

confidence: 99%

“…6C, G) and resembled the responses observed in infants and young children receiving bone-targeted, enzyme-replacement therapy for severe HPP. (30) Renal and testicular ultrasound studies revealed persistent, but surprisingly improved, testicular microlithiasis when compared to the postnatal images. Neither medullary nephrocalcinosis nor nephrolithiasis was present.…”

Section: Findings After Cessation Of Ehdp Therapymentioning

confidence: 94%

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Severe skeletal toxicity from protracted etidronate therapy for generalized arterial calcification of infancy

Otero

Gottesman

McAlister

et al. 2012

Journal of Bone and Mineral Research

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Generalized arterial calcification (AC) of infancy (GACI) is an autosomal recessive disorder that features hydroxyapatite deposition within arterial elastic fibers. Untreated, approximately 85% of GACI patients die by 6 months of age from cardiac ischemia and congestive heart failure. The first-generation bisphosphonate etidronate (EHDP; ethane-1-hydroxy-1,1-diphosphonic acid, also known as 1-hydroxyethylidene-bisphosphonate) inhibits bone resorption and can mimic endogenous inorganic pyrophosphate by blocking mineralization. With EHDP therapy for GACI, AC may resolve without recurrence upon treatment cessation. Skeletal disease is not an early characteristic of GACI, but rickets can appear from acquired hypophosphatemia or prolonged EHDP therapy. We report a 7-year-old boy with GACI referred for profound, acquired, skeletal disease. AC was gone after 5 months of EHDP therapy during infancy, but GACI-related joint calcifications progressed. He was receiving EHDP, 200 mg/day orally, and had odynodysphagia, diffuse opioid-controlled pain, plagiocephaly, facial dysmorphism, joint calcifications, contractures, and was wheelchair bound. Biochemical parameters of mineral homeostasis were essentially normal. Serum osteocalcin was low and the brain isoform of creatine kinase and tartrate-resistant acid phosphatase 5b (TRAP-5b) were elevated as in osteopetrosis. Skeletal radiographic findings resembled pediatric hypophosphatasia with pancranial synostosis, long-bone bowing, widened physes, as well as metaphyseal osteosclerosis, cupping and fraying, and ''tongues'' of radiolucency. Radiographic features of osteopetrosis included osteosclerosis and femoral Erlenmeyer flask deformity. After stopping EHDP, he improved rapidly, including remarkable skeletal healing and decreased joint calcifications. Profound, but rapidly reversible, inhibition of skeletal mineralization with paradoxical calcifications near joints can occur in GACI from protracted EHDP therapy. Although EHDP treatment is lifesaving in GACI, surveillance for toxicity is crucial. ß

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Section: Discussionmentioning

confidence: 99%

Section: Findings After Cessation Of Ehdp Therapymentioning

confidence: 94%

Severe skeletal toxicity from protracted etidronate therapy for generalized arterial calcification of infancy

Otero

Gottesman

McAlister

et al. 2012

Journal of Bone and Mineral Research

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“…Interestingly, hypophosphatasia can produce rickets‐like deformities as described here. Moreover, misshapen skulls, beading of costochondral junctions, enlarged joints from metaphyseal flaring and premature bony fusion of sutures can occur (Collmann, Mornet, Gattenlohner, Beck, & Girschick, 2009; Whyte, 2016), as well as, fractures and bone deformities (Whyte et al, 2012). …”

Section: Resultsmentioning

confidence: 99%

History and highlights of the teratological collection in the Museum Anatomicum of Leiden University, The Netherlands

Kim

Boek

Dam

et al. 2018

American J of Med Genetics Pt A

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The anatomical collection of the Anatomical Museum of Leiden University Medical Center (historically referred to as Museum Anatomicum Academiae Lugduno‐Batavae) houses and maintains more than 13,000 unique anatomical, pathological and zoological specimens, and include the oldest teratological specimens of The Netherlands. Throughout four centuries hundreds of teratological specimens were acquired by more than a dozen collectors. Due to the rich history of this vast collection, teratological specimens can be investigated in a unique retrospective sight going back almost four centuries. The entire 19th century collection was described in full detail by Eduard Sandifort (1742–1814) and his son Gerard Sandifort (1779–1848). Efforts were made to re‐describe, re‐diagnose and re‐categorize all present human teratological specimens, and to match them with historical descriptions. In the extant collection a total of 642 human teratological specimens were identified, including exceptional conditions such as faciocranioschisis and conjoined twins discordant for cyclopia, and sirenomelia. Both father and son Sandifort differed in their opinion regarding the causative explanation of congenital anomalies. Whereas, their contemporaries Wouter Van Doeveren (1730–1783) and Andreas Bonn (1738–1817) both presented an interesting view on how congenital anomalies were perceived and explained during the 18th and 19th centuries; the golden age of descriptive teratology. Although this enormous collection is almost 400 years old, it still impresses scientists, (bio)medical students, and laymen visiting and exploring the collections of the Museum Anatomicum in Leiden, The Netherlands.

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“…Two unrelated patients with worsening infantile HPP received marrow cell transplantations and survived a likely lethal outcome (Cahill et al 2007;Whyte et al 2003). Now, enzyme replacement therapy for severe HPP using human recombinant bone-targeted alkaline phosphatase provides promise for improved outcome (Whyte et al 2012).…”

Section: Discussionmentioning

confidence: 99%

“…The natural history of the perinatal and infantile forms of HPP has not been systematically reviewed or published. Recent reports of spontaneous postnatal improvement of skeletal deformities identified antenatally in some babies with "benign prenatal" HPP (Moore et al 1999;Pauli et al 1999;Wenkert et al 2011) and also in 2012, the potential of enzyme replacement treatment for the most severe forms of HPP (Whyte et al 2012) prompted review of our experience with this disease in Manitoba, Canada. We had previously reported that autosomal recessive HPP is especially prevalent in the Manitoba Mennonite population, and the molecular basis for the perinatal/early infantile form in the population is a founder mutation Gly334Asp in the TNSALP gene.…”

Section: Introductionmentioning

confidence: 99%

Outcome of Perinatal Hypophosphatasia in Manitoba Mennonites: A Retrospective Cohort Analysis

et al. 2013

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Hypophosphatasia (HPP) is the metabolic bone disease caused by loss-of-function mutation within the gene that encodes the "tissue nonspecific" isoenzyme of alkaline phosphatase (TNSALP). Perinatal HPP is usually fatal due to respiratory insufficiency, and infantile HPP often has a similar outcome although no formal study into the natural history of these severe forms of HPP has been undertaken. We reviewed our 80-year (1927-

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Enzyme-Replacement Therapy in Life-Threatening Hypophosphatasia

Abstract: Whyte, Michael P.; McAlister, William H.; and et al, ,"Enzyme-replacement therapy in life-threatening hypophosphatasia." The New England Journal of Medicine.366,10. 904-913. (2012).

Cited by 472 publications

References 30 publications

Severe skeletal toxicity from protracted etidronate therapy for generalized arterial calcification of infancy

Severe skeletal toxicity from protracted etidronate therapy for generalized arterial calcification of infancy

History and highlights of the teratological collection in the Museum Anatomicum of Leiden University, The Netherlands

Outcome of Perinatal Hypophosphatasia in Manitoba Mennonites: A Retrospective Cohort Analysis

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