Hypophosphatasia
Hypophosphatasia is a rare, hereditary, hitherto incurable disorder in bone metabolism, which manifests itself mainly in the skeletal structure. It is also referred to as Rathbun 's syndrome or Phosphatasemangelrachitis and often confused with other diseases such as rickets or osteoporosis, or " brittle bone disease" ( osteogenesis imperfecta ). However, due to inflammatory processes in bones, joints and muscles, it also comes to confusion with rheumatic diseases. The disease is inherited as an autosomal recessive trait.
Description
Multiple genetic features locus on chromosome 1 p34 -36, the reason that the enzyme alkaline phosphatase - More specifically, the tissue- nonspecific alkaline phosphatase (English TNSALP - for tissue non-specific alkaline phosphatase ) - at low concentrations in the organism is prepared and / or does not show enough activity. The alkaline phosphatase ( ALP) consists of several isoenzymes (but is usually only measured the total ALP in the blood), which are produced in different organs in the body and into the bone. There are specific ALPs ( intestinal type, placental type, pseudo- placental type) and a tissue- nonspecific ALP ( bone / liver / kidney type).
Alkaline phosphatase plays a significant role in the development of bone. The osteoblasts, which are the cells that build bone, require large amounts of alkaline phosphatase, some of which she produced herself and take part from the bloodstream for bone formation. The ALP splits among other inorganic pyrophosphate and so wins phosphate for bone formation. Together with calcium, the bone mineral hydroxyapatite is generated from it in the osteoblasts. Characterized in that the alkaline phosphatase in Hypophosphatasia is defective, is inorganic pyrophosphate, and accumulates in the organism actively inhibits further bone mineralization. At the same time calcium and phosphate connect with each other outside of the osteoblasts to form crystals, which can also distribute and accumulate in the organism. These microcrystals lead by an autoimmune response to inflammatory reactions in bones, joints and muscles. Above all, these non-bacterial inflammation of bones and joints often lead to confusion of the symptoms of hypophosphatasia with those of other diseases such as rheumatoid arthritis or osteoarthritis / arthritis ( and sometimes even with bone cancer).
In addition to the inorganic pyrophosphate also phosphoethanolamine and pyridoxal -5- phosphate in hypophosphatasia too little implemented and accumulate in the blood and / or urine, where they are used for reliable diagnosis of hypophosphatasia.
The research distinguishes five - according to other sources, six - has progressive forms of hypophosphatasia cells that have a very large variability in their clinical features ( phenotype).
The consequences of the lack of alkaline phosphatase are serious for the whole body: In infancy show deformities of the skull, by prematurely ossified cranial sutures. Due to soft bones in the chest it comes to problems with breathing. Almost all the bones can break or deform. This tendency increases with the mechanical load, such as when running. Since the growth plates of the bones are affected, short stature is also a common symptom of hypophosphatasia. In some cases, a real dwarfism occurs. The symptoms, however, are not limited only to the skeletal structure, but also affect other body functions such as digestion and nerve function. Also typical is a premature loss of both deciduous teeth and the permanent dentition. In some cases, a calcification of the kidney, called nephrocalcinosis observed.
Although it is inherited, the hypophosphatasia may occur for the first time at any age, or cause symptoms. During childhood, the confusion is close with various skeletal dysplasias, is in the adult patients, the first misdiagnosis usually osteoporosis.