Orodental phenotype and genotype findings in all subtypes of hypophosphatasia

Reibel, Amélie; Manière, Marie‐Cécile; Clauss, François; Droz, Dominique; Alembik, Yves; Mornet, Étienne; Bloch‐Zupan, Agnès

doi:10.1186/1750-1172-4-6

Cited by 102 publications

(93 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…According to the severity of the disorder, some dental defects were infrequent, whereas other are always present. 17 They consist of abnormal tooth shape (small bulbous crown, cervical constrictions and enlarged pulp spaces), abnormal tooth structure (enamel, dentin and cementum formation), tooth colour, dental anomalies of tooth eruption/exfoliation with premature loss of predominantly the primary and also the permanent dentition. Delayed eruption of teeth and primary teeth impaction (ankylosis) are also recorded.…”

Section: Clinical Specificity (Proportion Of Negative Tests If the DImentioning

confidence: 99%

Clinical utility gene card for: Hypophosphatasia – update 2013

et al. 2013

Self Cite

View full text Add to dashboard Cite

Section: Clinical Specificity (Proportion Of Negative Tests If the DImentioning

confidence: 99%

Clinical utility gene card for: Hypophosphatasia – update 2013

et al. 2013

Self Cite

View full text Add to dashboard Cite

“…HPP is characterized by subnormal plasma TNAP activity, leading to accumulation of the physiological substrates inorganic pyrophosphate (PP i ), a potent mineralization inhibitor [27], and pyridoxal-5′-phosphate (PLP), the major circulating form of vitamin B6 [35,42,45]. These biochemical changes underlie the most significant symptomatology in individuals with HPP: accumulation of PP i resulting in rickets in children or osteomalacia in adults [45], as well as dental defects [15,16,38]. The inability to produce pyridoxal (PL) from PLP leads to defective production of neurotransmitters such as g-aminobutyric acid (GABA) and serotonin, leading to seizures in the most severely affected patients [3,35,42].…”

Section: Introductionmentioning

confidence: 99%

Improvement of the skeletal and dental hypophosphatasia phenotype in Alpl−/− mice by administration of soluble (non-targeted) chimeric alkaline phosphatase

Gasque

Foster

Kuss

et al. 2015

Bone

View full text Add to dashboard Cite

Hypophosphatasia (HPP) results from ALPL gene mutations, which lead to a deficiency of tissue-nonspecific alkaline phosphatase (TNAP), and accumulation of inorganic pyrophosphate, a potent inhibitor of mineralization that is also a natural substrate of TNAP, in the extracellular space. HPP causes mineralization disorders including soft bones (rickets or osteomalacia) and defects in teeth and periodontal tissues. Enzyme replacement therapy using mineral-targeting recombinant TNAP has proven effective in preventing skeletal and dental defects in TNAP knockout (Alpl−/−) mice, a model for life-threatening HPP. Here, we show that the administration of a soluble, intestinal-like chimeric alkaline phosphatase (ChimAP) improves the manifestations of HPP in Alpl−/− mice. Mice received daily subcutaneous injections of ChimAP at doses of 1, 8 or 16 mg/kg, from birth for up to 53 days. Lifespan and body weight of Alpl−/− mice were normalized, and vitamin B6-associated seizures were absent with 16 mg/kg/day of ChimAP. Radiographs, μCT and histological analyses documented improved mineralization in cortical and trabecular bone and secondary ossification centers in long bones of ChimAP16-treated mice. There was no evidence of craniosynostosis in the ChimAP16-treated mice and we did not detect ectopic calcification by radiography and histology in the aortas, stomachs, kidneys or lungs in any of the treatment groups. Molar tooth development and function improved with the highest ChimAP dose, including enamel, dentin, and tooth morphology. Cementum remained deficient and alveolar bone mineralization was reduced compared to controls, though ChimAP-treated Alpl−/− mice featured periodontal attachment and retained teeth. This study provides the first evidence for the pharmacological efficacy of ChimAP for use in the treatment of skeletal and dental manifestations of HPP.

show abstract

“…After the first year, the childhood form of hypophosphatasia is characterized by short stature, bone deformities of the lower extremities, and premature loss of primary teeth [13,14]. The adult form of hypophosphatasia is mainly characterized by osteomalacia, pseudofractures, and pathologic fractures after minimal trauma, as well as by muscle and joint pain [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%