The phosphate diabetes is a disease in which the urine too much phosphate is excreted that are actually recovered in the kidney from the pre-urine would. This leads to severe bone growth disorders similar to rickets , because phosphate influences the storage of calcium in the bones. The disease manifests itself in early childhood and occurs on average in one in 325,000 people. Girls are affected twice as often as boys, but the disease progresses more easily. The probability of a so-called first mutation is approx. 1: 25,000,000. The disease is not contagious or communicable.
The disease is also known as familial hypophosphatemic rickets , vitamin D-resistant rickets or idiopathic Debré-de-Toni-Fanconi syndrome .
In phosphate diabetes, there is a mutation for a gene on the short arm of the X chromosome (Xp22.1). This mutation is dominant : one diseased allele is sufficient to trigger the disease. The exact mechanism of its formation is still unclear; It is assumed that the mutated gene contains the building instructions for a membrane protein that regulates the recovery of phosphate in the kidneys via fibroblast growth factor 23 (FGF-23). As a result of the mutation, this recovery is impaired by FGF-23 overactivity.
In the body, the amounts of phosphate and calcium dissolved in the blood are linked to one another (the so-called "calcium-phosphate product"). If the amount of phosphate in the blood drops, less calcium is built into the bones. However, this calcium is needed in large quantities for the strength of the bones, and the bones can no longer cope with the higher loads caused by the growing child. This leads to the bone deformations that are typical for the disease.
In addition, too low a phosphate level in a healthy body would trigger the release of vitamin D ( calcitriol ), which in turn leads to an increase in phosphate absorption from the intestine. In the case of phosphate diabetes, however, this control cycle is also disturbed: Despite the reduced phosphate level in the serum, the calcitriol secretion does not increase.
The disease usually manifests itself from the age of two in the form of skeletal deformities with strong genoa and coxa vara (bow legs), wide-legged waddling gait, short stature , impaired tooth development and - if no treatment is given - middle ear hearing loss due to the deficient development of the ossicles.
As a secondary disease, calcium deposits can form in the kidneys.
The clinical picture, the age at which the first symptoms appear and the family history of phosphate diabetes are typical.
The clinical picture is determined in particular by analyzing blood values and evaluating x-rays. The blood shows a decreased phosphate level, an increased alkaline phosphatase with normal levels for calcium, parathyroid hormone and calcitriol.
In the differential diagnosis, it must be ensured that the clinical picture of phosphate diabetes can easily be confused with that of hypophosphatasia . In this case, however, the alkaline phosphatase level is lowered, so that another treatment is necessary.
Therapy for phosphate diabetes is symptomatic and consists of the administration of phosphate tablets and calcitriol . Therapy should be started as early as possible to avoid skeletal damage. Because of the risk of permanent kidney damage as a result of the therapy ( nephrocalcinosis ), regular ultrasound checks should be carried out on the kidneys . A specific drug, the monoclonal antibody burosumab (Crysvita ® ), which is directed against FGF-23, has been available since April 2018 .
With timely treatment, severe bone deformities can be prevented. If treatment is started late, orthopedic corrections may be necessary.
- Alphabetical directory for the ICD-10-WHO version 2019, volume 3. German Institute for Medical Documentation and Information (DIMDI), Cologne, 2019, p. 699
- Farzana Perwad, Martin YH Zhang, Harriet S. Tenenhouse, Anthony A. Portale: Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro . In: American Journal of Physiology. Renal Physiology . tape 293 , no. 5 , November 2007, ISSN 1931-857X , p. F1577–1583 , doi : 10.1152 / ajprenal.00463.2006 , PMID 17699549 .
- Avoxa Media Group Deutscher Apotheker GmbH: Burosumab | Crysvita® | 68 | 2018. Retrieved January 6, 2019 .