[Hypophosphatasia].
Hypophosphatasia (HP) is an inborn error of bone metabolism transmitted predominantly as an autosomal-recessive trait. It is characterized by a reduced activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSAP) and elevated concentrations of its substrates, including pyrophosphates. Clinical symptoms include defective bone mineralisation with bone deformities, fractures and as recently defined chronic non-bacterial osteomyelitis. Renal damage due to calcification, craniosynostosis and dental abnormalities with premature loss of dentition are further symptoms, which have been described as characteristic in the ESPED inquiry of 2004. Knowledge about the mechanisms underlying cell activation leading to inflammation and tissue destruction is still limited in HP. Recent investigations have provided evidence that calcium pyrophosphate crystals are essentially involved in activating inflammatory signal transduction pathways via different receptors of the innate immune system. Laboratory assays, genetic counselling and testing, and radiologic imaging can confirm the diagnosis. Because symptoms are highly variable in their clinical expression, patients should be followed by a HP-experienced multidisciplinary team (paediatrician, radiologist, orthopedist, neurosurgeon, dentist). At the moment symptomatic support and treatment is most important because a causative therapy, e. g. enzyme replacement therapy, is not yet available.
Beck
C
C
Bereiche Immunologie, Infektiologie, Hämostasiologie, Rheumatologie, Osteologie und Gastroenterologie, Kinderklinik und Poliklinik des Universitätsklinikums, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Morbach
H
H
Stenzel
M
M
Schneider
P
P
Collmann
H
H
Girschick
G
G
Girschick
H J
HJ
D000469:Alkaline Phosphatase / Q000172:deficiency / Q000235:genetics; D001848:Bone Diseases, Developmental / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D003299:Cooperative Behavior; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D007014:Hypophosphatasia / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D007223:Infant; D033183:Interdisciplinary Communication; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics; D010348:Patient Care Team; D010641:Phenotype
D007527:Isoenzymes; D000469:Alkaline Phosphatase