China
Africa
Explore chapters and articles related to this topic
Real-World Data and Real-World Evidence
Published in Wei Zhang, Fangrong Yan, Feng Chen, Shein-Chung Chow, Advanced Statistics in Regulatory Critical Clinical Initiatives, 2022
The approval of Asfotase alfa for patients with the perinatal and infantile forms of HPP, was based on comparison of 68 treated patients from two multicenter, multinational, single-arm, interventional studies, with 48 patients with similar characteristics from a retrospective natural history study, who served as another type of external control74,75. These controls were patients diagnosed with or treated for severe pediatric hypophosphatasia at academic medical centers, whose data were obtained using a retrospective chart review of medical records75.
Hypophosphatasia
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Discovery of the gene (ALPL) that is defective in hypophosphatasia has clarified the genetics of this condition. It is clear that the classic mild hypophosphatasia, including asymptomatic people who have phosphoethanolaminuria and some with odontohypophosphatasia have dominant expression of mutation on a single allele [7, 50–52].
Biocatalytic Nanoreactors for Medical Purposes
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Oscar González-Davis, Chauhan Kanchan, Rafael Vazquez-Duhalt
Hypophosphatasia is osteomalacia caused by mutations in the gene that encodes the alkaline phosphatase (ALP) that affects the development of bones and teeth (Whyte, 2010; Mornet, 2018). The ALP deficiency disrupts a process called mineralization, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth. The ERT is now available for hypophosphatasia. Asfotase alfa is a recombinant glycoprotein that contains the catalytic domain (the active site) of tissue-nonspecific alkaline phosphatase. Asfotase alfa therapy improved skeletal, respiratory, and physical symptoms with only a few severe side effects in patients with hypophosphatasia, supporting the safety and efficacy of ERT (Kitaoka et al., 2017; Whyte, 2017).
The use of alkaline phosphatase as a bone turnover marker after spinal cord injury: A scoping review of human and animal studies
Published in The Journal of Spinal Cord Medicine, 2023
Matteo Ponzano, Matheus J. Wiest, André Coleman, Emily Newton, Maureen Pakosh, Eleni M. Patsakos, David S. K. Magnuson, Lora M. Giangregorio, B. Catharine Craven
Serum ALP is a common BTM for screening for heterotopic ossification (HO), even though HO may also present with normal serum ALP levels,22 and some studies did not show associations between serum ALP levels and HO.23–26 Conversely, low levels of ALP represent a hallmark of hypophosphatasia, a rare disorder that alters mineralization of bone and teeth, causing low BMD, joint pain and loss of secondary teeth.27 Bone-specific alkaline phosphatase (B-ALP) is an isoform of ALP found in the bone tissue, which degrades the mineralization inhibitor pyrophosphate with alkaline pH conditions, and its presence on the osteoblasts’ membrane is required for bone mineralization.28 B-ALP is an appropriate marker of bone formation given its slow clearance, low intra-individual variability and role in the calcification process.29–31 High levels of serum B-ALP predict spine and non-spine fracture in able-bodied individuals,32 while the evidence on hip fractures is conflicting.33,34 However, there is uncertainty regarding the response of B-ALP following SCI, and the evidence regarding changes in B-ALP after SCI and its role in bone loss is heterogeneous and conflicting. Furthermore, there is the need to explore what has been done, to date, in terms of populations and methodologies used to study B-ALP across the SCI population.
Prenatal diagnosis facilitated prompt enzyme replacement therapy for prenatal benign hypophosphatasia
Published in Journal of Obstetrics and Gynaecology, 2020
Yuka Ishijima, Takashi Iizuka, Kyosuke Kagami, Sakiko Masumoto, Kyohei Nakade, Yusuke Mitani, Yo Niida, Atsushi Watanabe, Rena Yamazaki, Masanori Ono, Hiroshi Fujiwara
Hypophosphatasia (HPP) is a rare disorder which is caused by loss of function mutations within the alkaline phosphatase, liver/bone/kidney gene (ALPL), which encodes the tissue non-specific isoenzyme of alkaline phosphatase (Iqbal et al. 2000). HPP is classified into six subtypes based on the onset and severity of skeletal dysplasia. The six clinical types of HPP are the following: (1) perinatal lethal, and (2) prenatal benign, which are apparent at birth, (3) infantile, from 1 to 6 months, (4) childhood type, from the age of 6 months to 18 years, (5) odonto type, which is characterised by the premature loss of deciduous teeth by 5 years without apparent bone symptoms, and (6) adult, which is typically presents during middle age. The perinatal lethal type is usually lethal because of a profound reduction in osteogenesis (Taketani et al. 2014). About 50% of infantile HPP die early, whereas prenatal benign HPP has a good prognosis. Because infantile HPP and perinatal lethal HPP show poor prognosis, they are often referred as ‘life-threatening’ HPP. Perinatal lethal and infantile HPP have poor prognosis due to respiratory issues, whereas perinatal benign HPP is the good prognostic subtype which does not involve respiratory issues and skeletal hypoplasia spontaneously improves in some cases (Whyte et al. 2016).
Pediatric reference intervals for general clinical chemistry components – merging of studies from Denmark and Sweden
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2018
Peter Ridefelt, Linda Hilsted, Anders Juul, Dan Hellberg, Pål Rustad
Interpretation of alkaline phosphatase activity in children is challenging due to extensive changes with growth and puberty leading to distinct sex- and age-specific dynamics [26]. The present study gave similar results as the CALIPER project and the Loh and Metz’s study [2,6], with a slowly increasing level up to 10 years of age, and then peaks during puberty with females peaking at slightly lower age (Figure 3). These peaks call for extensive partitioning for age and highlight the problem of representing the age and gender dependence of alkaline phosphatase concentrations with distinct age groups. Continuous reference intervals would likely capture the changes during puberty more accurately than discrete age groups. Thus, some of the differences between the present study and the CALIPER, particularly between 13 and 16 years of age, might be due to the specific age groups chosen for partitioning of the ALP peak during puberty. All laboratories do not report alkaline phosphatase results with lower limits for the reference interval. The presently suggested intervals include lower limits to draw attention to the abnormally low levels of ALP associated with hypophosphatasia, a rare inborn error of metabolism causing bone disease [27].