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Connie Y Chang, Daniel I Rosenthal, Deborah M Mitchell, Atsuhiko Handa, Susan V Kattapuram, Ambrose J Huang
Metabolic bone diseases are a diverse group of diseases that result in abnormalities of (a) bone mass, (b) structure mineral homeostasis, (c) bone turnover, or (d) growth. Osteoporosis, the most common metabolic bone disease, results in generalized loss of bone mass and deterioration in the bone microarchitecture. Impaired chondrocyte development and failure to mineralize growth plate cartilage in rickets lead to widened growth plates and frayed metaphyses at sites of greatest growth. Osteomalacia is the result of impaired mineralization of newly formed osteoid, which leads to characteristic Looser zones...
October 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
(no author information available yet)
No abstract text is available yet for this article.
November 2016: International Journal of Paediatric Dentistry
Michael P Whyte, Katherine L Madson, Dawn Phillips, Amy L Reeves, William H McAlister, Amy Yakimoski, Karen E Mack, Kim Hamilton, Kori Kagan, Kenji P Fujita, David D Thompson, Scott Moseley, Tatjana Odrljin, Cheryl Rockman-Greenberg
Background. Hypophosphatasia (HPP) is caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Consequently, cell-surface deficiency of TNSALP phosphohydrolase activity leads to extracellular accumulation of inorganic pyrophosphate, a natural substrate of TNSALP and inhibitor of mineralization. Children with HPP can manifest rickets, skeletal pain, deformity, fracture, muscle weakness, and premature deciduous tooth loss. Asfotase alfa is a recombinant, bone-targeted, human TNSALP injected s...
June 16, 2016: JCI Insight
Thomas J Weber, Eileen K Sawyer, Scott Moseley, Tatjana Odrljin, Priya S Kishnani
BACKGROUND: Hypophosphatasia (HPP) is a rare metabolic bone disease caused by loss-of-function mutation(s) in the tissue-nonspecific alkaline (TNSALP) phosphatase gene, which manifests as rickets and/or osteomalacia with systemic complications and affects patients of all ages. The burden of disease is poorly characterized in adult patients. AIMS: We assessed patient-reported burden of disease using two surveys reasonably specific for HPP symptomatology, the Hypophosphatasia Impact Patient Survey (HIPS) and the Hypophosphatasia Outcomes Study Telephone interview (HOST)...
October 2016: Metabolism: Clinical and Experimental
Pervaiz Ali Channar, Syed Jawad Ali Shah, Sidra Hassan, Zaib Un Nisa, Joanna Lecka, Jean Sévigny, Jürgen Bajorath, Aamer Saeed, Jamshed Iqbal
A series of isonicotinohydrazides derivatives were synthesized and tested against recombinant human and rat ecto-5'-nucleotidases (h-e5'NT & r-e5'NT) and alkaline phosphatase isozymes including both bovine tissue-nonspecific alkaline phosphatase (b-TNAP) and tissue specific calf intestinal alkaline phosphatase (c-IAP). These enzymes are implicated in vascular calcifications, hypophosphatasia, solid tumors and cancers, such as colon, lung, breast, pancreas and ovary. All tested compounds were active against both enzymes...
September 2, 2016: Chemical Biology & Drug Design
B L Foster, P Kuss, M C Yadav, T N Kolli, S Narisawa, L Lukashova, E Cory, R L Sah, M J Somerman, J L Millán
Loss-of-function mutations in ALPL result in hypophosphatasia (HPP), an inborn error of metabolism that causes defective skeletal and dental mineralization. ALPL encodes tissue-nonspecific alkaline phosphatase, an enzyme expressed in bone, teeth, liver, and kidney that hydrolyzes the mineralization inhibitor inorganic pyrophosphate. As Alpl-null mice die before weaning, we aimed to generate mouse models of late-onset HPP with extended life spans by engineering a floxed Alpl allele, allowing for conditional gene ablation (conditional knockout [cKO]) when crossed with Cre recombinase transgenic mice...
August 31, 2016: Journal of Dental Research
Michael P Whyte, Deborah Wenkert, Fan Zhang
Hypophosphatasia (HPP) is the inborn-error-of-metabolism that features deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Resultant extracellular accumulation of inorganic pyrophosphate, a TNSALP substrate and potent inhibitor of mineralization, typically leads to tooth loss and sometimes to rickets or osteomalacia. HPP's remarkably broad-ranging severity is largely explained by autosomal dominant versus autosomal recessive transmission from among several hundred usually missense mutations positioned throughout the gene that encodes TNSALP...
August 27, 2016: Bone
R Okawa, O Iijima, M Kishino, H Okawa, S Toyosawa, H Sugano-Tajima, T Shimada, T Okada, K Ozono, T Ooshima, K Nakano
BACKGROUND AND OBJECTIVE: Hypophosphatasia is a rare inherited skeletal disorder characterized by defective bone mineralization and deficiency of tissue non-specific alkaline phosphatase (TNSALP) activity. The disease is caused by mutations in the liver/bone/kidney alkaline phosphatase gene (ALPL) encoding TNSALP. Early exfoliation of primary teeth owing to disturbed cementum formation, periodontal ligament weakness and alveolar bone resorption are major complications encountered in oral findings, and discovery of early loss of primary teeth in a dental examination often leads to early diagnosis of hypophosphatasia...
August 26, 2016: Journal of Periodontal Research
Michele Abate, Vincenzo Salini, Isabel Andia
Congenital metabolic disorders are consequence of defects involving single genes that code for enzymes. Blocking metabolic pathways, the defect leads to the shortage of essential compounds, and/or to the accumulation of huge quantities of precursors, which interfere with normal functions. Only few of these diseases are characterized by a clinically significant tendon involvement.Heterozygous Familial Hypercholesterolaemia results from the inheritance of a mutant low-density lipoprotein receptor gene; patients show high cholesterol levels, precocious coronary artery disease, and may develop tendon xanthomata (mainly in Achilles tendon)...
2016: Advances in Experimental Medicine and Biology
Zhu-Yu Wang, Kai Zhang, Guang-Sen Zheng, Wei Qiao, Yu-Xiong Su
BACKGROUND: Hypophosphatasia is a rare inherited disease derived from mutations in tissue non-specific alkaline phosphatase genes, with typical oral symptoms including short root anomaly and dysplasia of dentin or cementum. CASE PRESENTATION: Two young female patients presented with short root anomaly with a history of premature loss of deciduous and/or permanent teeth. The laboratory and imaging investigations were performed. One case was diagnosed as odontohypophosphatasia concurrent with hyperthyroidism, the other was odontohypophosphatasia concurrent with multiple radicular cysts...
2016: BMC Oral Health
Timothy Bhattacharyya, Smita Jha, Hongying Wang, Daniel L Kastner, Elaine F Remmers
BACKGROUND: Case reports have linked adult hypophosphatasia as a possible cause of atypical femur fractures (AFF) associated with bisphosphonate use. Adult hypophosphatasia is an asymptomatic genetic condition which results in low alkaline phosphatase and elevated pyridoxal phosphate. We conducted a case-control study to assess the role of hypophosphatasia and atypical femur fracture. METHODS: We recruited 13 control patients who took long term bisphosphonates without complication and 10 patients who sustained atypical femur fractures (mean bisphosphonate use, 9 years both cohorts)...
2016: BMC Musculoskeletal Disorders
Álvaro Sebastián-Serrano, Tobias Engel, Laura de Diego-García, Luis A Olivos-Oré, Marina Arribas-Blázquez, Carlos Martínez-Frailes, Carmen Pérez-Díaz, José Luis Millán, Antonio R Artalejo, María Teresa Miras-Portugal, David C Henshall, Miguel Díaz-Hernández
Hypomorphic mutations in the gene encoding the tissue-nonspecific alkaline phosphatase (TNAP) enzyme, ALPL in human or Akp2 in mice, cause hypophosphatasia (HPP), an inherited metabolic bone disease also characterized by spontaneous seizures. Initially, these seizures were attributed to the impairment of GABAergic neurotransmission caused by altered vitamin B6 (vit-B6) metabolism. However, clinical cases in human newborns and adults whose convulsions are refractory to pro-GABAergic drugs but controlled by the vit-B6 administration, suggest that other factors are involved...
July 27, 2016: Human Molecular Genetics
(no author information available yet)
No abstract text is available yet for this article.
2016: Medical Letter on Drugs and Therapeutics
Dawn Phillips, Laura E Case, Donna Griffin, Kim Hamilton, Sergio Lerma Lara, Beth Leiro, Jessica Monfreda, Elaine Westlake, Priya S Kishnani
Hypophosphatasia (HPP) is a rare inborn error of metabolism resulting in undermineralization of bone and subsequent skeletal abnormalities. The natural history of HPP is characterized by rickets and osteomalacia, increased propensity for bone fracture, early loss of teeth in childhood, and muscle weakness. There is a wide heterogeneity in disease presentation, and the functional impact of the disease can vary from perinatal death to gait abnormalities. Recent clinical trials of enzyme replacement therapy have begun to offer an opportunity for improvement in survival and function...
September 2016: Molecular Genetics and Metabolism
C Hofmann, L Seefried, F Jakob
Hypophosphatasia (HPP) is a rare disease caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase (TNAP, TNSALP) gene. HPP causes a multisystemic syndrome with a predominant bone phenotype. The clinical spectrum ranges from high lethality in early onset (<6 months) HPP to mild late-onset syndromes. HPP management so far has been only supportive. Subcutaneous asfotase alfa, a first-in-class bone-targeted human TNAP enzyme replacement therapy, is the first compound to be approved for long-term treatment of bone manifestations in pediatric-onset HPP...
May 2016: Drugs of Today
Eu Gene Park, Sung Yoon Cho, Jeehun Lee, Jihyun Kim, Heeyeon Cho, Jinsup Kim, Rimm Huh, Chang-Seok Ki, Ok-Hwa Kim, Dong-Kyu Jin
Hypophosphatasia is a rare hereditary disorder characterized by defective bone and tooth mineralization and deficiency of tissue non-specific alkaline phosphatase activity. The prognosis for the infantile form is poor, with approximately 50% of patients dying within the first year of life from respiratory failure. We describe the clinical and biochemical findings as well as the molecular analysis of a Korean boy with infantile hypophosphatasia and present a literature review. A 1-month-old boy visited the clinic because of poor feeding, frequent vomiting, hypotonia, and failure to thrive from birth...
May 2016: Annals of Clinical and Laboratory Science
N Sharma, E Bache, T Clare
INTRODUCTION: We report a case of an adolescent sustaining bilateral femoral neck fractures due to a first time epileptic seizure, as a result of expansion of his known syrinx. CASE REPORT: A 19-year-old patient suffering from hypophosphatasia (HPP), Arnold-Chiari malformation, and a ventriculoperitoneal shunt sustained a trivial fall with profound pain and an inability to mobilize. Radiographs demonstrated a right-sided Garden-4 femoral neck and left-sided multi-fragmentary intracapsular/extracapsular fractures...
July 2015: Journal of Orthopaedic Case Reports
Hideo Orimo
Hypophosphatasia (HPP) is an inherited systemic bone disease that is characterized by bone hypomineralization. HPP is classified into six forms according to the age of onset and severity as perinatal (lethal), perinatal benign, infantile, childhood, adult, and odontohypophosphatasia. The causative gene of the disease is the ALPL gene that encodes tissue-nonspecific alkaline phosphatase (TNAP). TNAP is expressed ubiquitously, and its physiological role is apparent in bone mineralization. A defect in bone mineralization can manifest in several ways, including rickets or osteomalacia in HPP patients...
2016: Therapeutics and Clinical Risk Management
E M Olech, T Zemojtel, A Sowińska-Seidler, S Mundlos, P N Robinson, M Karczewski, A Jamsheer
Lethal skeletal disorders represent a heterogeneous and clinically variable group of genetic conditions, usually difficult to diagnose without post-mortem radiological assessment. Here we report on a stillborn patient delivered at 22 weeks of gestation who presented with severe skeletal symptoms comprising limb shortening and intrauterine fractures detected upon prenatal ultrasound and autopsy examination. Since post-mortem X-ray was refused and no phenotypic diagnosis could be attempted, we performed next-generation sequencing (NGS) of 2741 genes associated with all known Mendelian disorders...
March 2016: Polish Journal of Pathology: Official Journal of the Polish Society of Pathologists
Sophie Collardeau-Frachon, Marie-Pierre Cordier, Massimiliano Rossi, Laurent Guibaud, Christine Vianey-Saban
This review highlights the importance of performing an autopsy when faced with fetal abortion or termination of pregnancy with suspicion of an inborn error of metabolism. Radiological, macroscopic and microscopic features found at autopsy as well as placental anomalies that can suggest such a diagnosis are detailed. The following metabolic disorders encountered in fetuses are discussed: lysosomal storage diseases, peroxisomal disorders, cholesterol synthesis disorders, congenital disorders of glycosylation, glycogenosis type IV, mitochondrial respiratory chain disorders, transaldolase deficiency, generalized arterial calcification of infancy, hypophosphatasia, arylsulfatase E deficiency, inborn errors of serine metabolism, asparagine synthetase deficiency, hyperphenylalaninemia, glutaric aciduria type I, non-ketotic hyperglycinemia, pyruvate dehydrogenase deficiency, pyruvate carboxylase deficiency, glutamine synthase deficiency, sulfite oxidase and molybdenum cofactor deficiency...
September 2016: Journal of Inherited Metabolic Disease
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