Hypophosphatasia

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Classification according to ICD-10
E83.38 Disorders of phosphorus metabolism and phosphatase
hypophosphatasia
ICD-10 online (WHO version 2019)

Hypophosphatasia ( HPP for short ) is a rare, hereditary , currently incurable disorder in bone metabolism, which manifests itself primarily in the skeletal structure . It is also referred to as Rathbun syndrome or phosphatase deficiency rickets and is often confused with other diseases such as rickets or osteoporosis or "glass bone disease" ( osteogenesis imperfecta ). However, inflammatory processes in bones, joints and muscles also lead to confusion with rheumatic diseases . The disease is autosomal - recessive inherited.

description

Several genetic specifics on chromosome 1 gene locus p34-36 are the reason that the enzyme alkaline phosphatase - more specifically, the tissue-nonspecific alkaline phosphatase ( engl. TNSALP - for tissue non-specific alkaline phosphatase ) - in too low a concentration in the organism and / or shows insufficient activity. Alkaline phosphatase ( ALP ) consists of several isoenzymes (but mostly only the total ALP in the blood is measured ), which are produced in different organs in the body and in the bones . There are specific ALPs ( intestinal type , placental type , pseudo-placental type ) and a tissue-unspecific ALP ( bone / liver / kidney type ).

Alkaline phosphatase plays an essential role in building bones. The osteoblasts , the cells that build the bones, need large amounts of alkaline phosphatase to build bones, some of which they produce themselves and some of which they take from the bloodstream. The ALP breaks down, among other things, inorganic pyrophosphate and thus wins phosphate for bone structure. Together with calcium , the bone mineral hydroxyapatite is generated in the osteoblasts . Because the alkaline phosphatase is defective in hypophosphatasia, inorganic pyrophosphate accumulates in the organism and actively inhibits further bone mineralization. At the same time, calcium and phosphate combine to form crystals outside the osteoblasts, which can also spread and be deposited in the body. By means of an autoimmune reaction, these microcrystals lead to inflammatory reactions in bones, joints and muscles. This non-bacterial inflammation of the bones and joints in particular often confuses the symptoms of hypophosphatasia with those of other diseases such as rheumatism or osteoarthritis / arthritis (and sometimes even bone cancer ).

In addition to the inorganic pyrophosphate, phosphoethanolamine and pyridoxal-5-phosphate are not converted enough in hypophosphatasia and accumulate in the blood and / or urine, where they are used for the reliable diagnosis of hypophosphatasia.

Research differentiates a total of five - according to other sources, six - course forms of hypophosphatasia, which therefore show a very large variability in terms of their clinical appearance ( phenotype ).

The consequences of the lack of alkaline phosphatase are serious for the entire body: In infancy , deformities of the skull appear due to prematurely ossified skull sutures. If the bones in the rib cage are too soft, breathing problems arise . Almost all bones can break or become deformed. This tendency increases with the mechanical load, for example when running. Since the growth plates of the bones are also affected, short stature is also a common symptom of hypophosphatasia. In some cases there is also a real short stature . However, the symptoms are not limited to the structure of the skeleton, but also affect other body functions such as digestion and nerve function . Also typical is a premature loss of both deciduous teeth and the second dentition. In some cases, calcification of the kidneys , called nephrocalcinosis, can also be observed.

Although it is inherited, hypophosphatasia can appear for the first time at any age or cause symptoms. While it is likely to be mistaken for various skeletal dysplasias in childhood , the first misdiagnosis in adult patients is usually osteoporosis .

history

In 1956 Heinz Nierhoff and Otto Huebner published a description of the infantile form of hypophosphatasia.

The outdated term Nierhoff-Huebner syndrome refers to this .

literature

Individual evidence

  1. ↑ P. Matzen: www.hypophosphatasie.net.
  2. ↑ H. Nierhoff, O. Hübner: Familial systemized enchondral dysostosis in 3 siblings. In: Journal of Pediatrics. Vol. 78, No. 5, 1956, pp. 497-521, PMID 13423511 .
  3. ↑ Bernfried Leiber (founder): The clinical syndromes. Syndromes, sequences and symptom complexes . Ed .: G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger. 7., completely reworked. Edition. tape 2 : symptoms . Urban & Schwarzenberg, Munich et al. 1990, ISBN 3-541-01727-9 .

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