Clinical utility gene card for: hypophosphatasia

Mornet, Étienne; Beck, Christine R.; Bloch‐Zupan, Agnès; Girschick, Hermann; Merrer, Martine Le

doi:10.1038/ejhg.2010.170

Cited by 23 publications

(13 citation statements)

References 26 publications

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“…Clinical variability has been explained by the "severity" of different mutations. However, the course of disease may vary in subjects within the same family carrying the same genotype [78].…”

Section: Hypophosphatasiamentioning

confidence: 99%

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Autoinflammatory bone disorders

Morbach

Hedrich

Beer

et al. 2013

Clinical Immunology

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Section: Hypophosphatasiamentioning

confidence: 99%

“…It is characterized by a defect in the tissue nonspecific alkaline phosphatase gene (TNSALP) which results in elevated concentrations of its substrates, including pyrophosphates [78]. Defective bone mineralization and resulting bone deformities and fractures are the leading symptoms of this disease.…”

Section: Hypophosphatasiamentioning

confidence: 99%

Autoinflammatory bone disorders

Morbach

Hedrich

Beer

et al. 2013

Clinical Immunology

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“…The inheritance mechanism can be autosomal recessive or dominant. About 80 % of the known mutations are missense point mutations, 10 % are small deletions, 4 % splicing mutations, 3 % nonsense mutations, 2 % small insertions, and ≤1 % complex insertion/deletions, large deletions, or mutations in the regulatory sequence [21,23,24].…”

Section: Geneticsmentioning

confidence: 99%

Hypophosphatasia: an overview of the disease and its treatment

Bianchi

2015

Osteoporos Int

108

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This review presents the current knowledge on hypophosphatasia, a rare genetic disease of very variable severity (from lethal to mild) and clinical presentation, caused by defective production of tissue-non-specific alkaline phosphatase (TNSALP). Hypophosphatasia can affect babies in utero as well as infants, children, and adults. The article first presents the genetics of TNSALP and its many known mutations underlying the disease. Then, it presents the epidemiology, classification, and clinical presentation of the six different forms of the disease (perinatal lethal, prenatal benign, infantile, childhood, adult, and odontohypophosphatasia) as well as the essential diagnostic clues. The last section on treatment presents a survey of the therapeutic approaches, up to the ongoing phase 2 studies of enzyme replacement therapy.

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“…In bone, it is essential for the mineralization process, because it hydrolyzes pyrophosphate, an inhibitor of hydroxyapatite formation and, at the same time, releases inorganic phosphate, which combines with calcium to promote mineralization . To date, at least 397 variants have been described in this gene as causing HPP (as reported in The Tissue Nonspecific Alkaline Phosphatase Gene Mutation Database) . Most are missense mutations found in homozygous or compound heterozygous form.…”

Section: Introductionmentioning

confidence: 99%

Loss-of-Function Mutations in the ALPL Gene Presenting with Adult Onset Osteoporosis and Low Serum Concentrations of Total Alkaline Phosphatase

Alonso

Larraz-Prieto

Berg

et al. 2019

Journal of Bone and Mineral Research

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Hypophosphatasia (HPP) is a rare inherited disorder characterized by rickets and low circulating concentrations of total alkaline phosphatase (ALP) caused by mutations in ALPL. Severe HPP presents in childhood but milder forms can present in adulthood. The prevalence and clinical features of adult HPP are poorly defined. The aim of this study was to evaluate the prevalence and clinical significance of low serum total alkaline phosphatase (ALP) levels in a clinic‐based population of adult osteoporotic patients. We searched for patients with low ALP in a cohort of 3285 patients referred to an osteoporosis clinic over a 10‐year period and performed mutation screening of ALPL in those with low ALP (≤40 U/L) on two or more occasions. These individuals were matched with four clinic controls with a normal ALP. We also evaluated the prevalence of low ALP and ALPL mutations in 639 individuals from the general population from the same region. We identified 16/3285 (0.49%) clinic patients with low ALP and 14 (87.5%) had potentially pathogenic variants in ALPL. Eight of these individuals were heterozygous for mutations previously described in HPP and 2 were heterozygous for novel mutations (p.Arg301Trp and p.Tyr101X). These mutations were not found in clinic controls or in the general population. Eight patients with low ALP, including 4 with ALPL mutations, were treated with bisphosphonates for an average of 6.5 years. In these individuals, the rate of fractures during treatment was comparable to that in normal ALP clinic controls who were treated with bisphosphonates. We conclude that heterozygous loss‐of‐function mutations in ALPL are common in osteoporosis patients with low ALP. Further studies are required to determine how best these individuals should be treated. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

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Clinical utility gene card for: hypophosphatasia

Cited by 23 publications

References 26 publications

Autoinflammatory bone disorders

Autoinflammatory bone disorders

Hypophosphatasia: an overview of the disease and its treatment

Loss-of-Function Mutations in the ALPL Gene Presenting with Adult Onset Osteoporosis and Low Serum Concentrations of Total Alkaline Phosphatase

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