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  • Kiara Sahi

X-Linked Hypophosphatemia.

By: Kiara Sahi, Contributing Writer

Edited by: Fauzia Haque, Editor; Elias Azizi, Editor in Chief

Let’s talk about phosphorus.

Phosphorus is the second most abundant mineral present in the human body, and the role it plays in the normal functioning of the body is crucial. Phosphorus is an integral component of RNA, DNA, and phospholipids. It behaves as a regulator of intracellular signalling as well as a source of the bonds formed in adenosine triphosphates and finally, it plays a critical role in bone development during childhood and maintains bone and tooth strength during adulthood. It is this final function, that is, the relevance of phosphorus to our bones and teeth, that will be explored in this article.

From the aforementioned significance of phosphorus to our body, it becomes abundantly clear that the homeostasis of phosphorus at a cellular level is of utmost importance. Thus, in order to maintain a proper balance of phosphorus in the blood, an adequate dietary intake of the mineral is recommended (NCBI).

However, whenever there is an imbalance in phosphate levels, particularly when the phosphate levels in the blood are low, an adverse problem comes to light : X-linked hypophosphatemia.

What is X-linked hypophosphatemia?

According to Medline, X-linked hypophosphatemia, also known as hereditary hypophosphatemic rickets, is an inherited condition that occurs due to low phosphate levels in the blood. The symptoms that are exhibited as a result of this disorder vary from individual to individual. While some individuals who are mildly affected by the disorder may show little to no symptoms, more severely affected individuals will show stunted growth, bone abnormalities, such as knock knees, which may cause bone pain during movement and can worsen if left untreated due to weight-bearing activities, dental pain, abscesses, and several other oral manifestations. Other symptoms include craniosynostosis, softening of bones (usually seen in adults), and abnormal bone development in the areas where tendons and ligaments attach to joints.

While a diagnosis is usually made during early childhood, some cases go undetected until adulthood due to the variable presentation of the disorder (American Dental Association).

Why is it called “X-linked” hypophosphatemia?

The most common type of hypophosphatemia has an X-linked dominant pattern of inheritance. This means that the gene that is responsible for the disorder is located on the X-chromosome and is the dominant gene.

PHEX (Phosphate Regulating Endopeptidase Homolog X-Linked) is a gene that carries the instructions for the synthesis of an enzyme that is active in bones and teeth. This gene is either directly or indirectly concerned with the regulation of a protein known as fibroblast growth factor 23. This protein essentially hinders the reabsorption of phosphate into the bloodstream, and PHEX gene mutations lead to the overproduction of fibroblast growth factor 23. This causes a severe deficiency of phosphate in the blood and thus leads to the aforementioned symptoms. However, the clear and defined role that the PHEX gene plays in terms of phosphate levels in the blood is yet to be ascertained (Medline).

The PHEX gene is carried on the ‘X’ chromosome. Males have one X chromosome, while females have two X chromosomes. Since this is an X-linked dominant pattern of inheritance, the presence of a mutation in one of the two copies in females, and in the only copy in males, is enough to cause the disorder. This disorder, however, cannot be passed on from a father to their son.

Treatment of X-linked hypophosphatemia.

The oral administration of phosphate three to five times daily along with high dose calcitriol is routine treatment of X linked hypophosphatemia. Since the disorder increases the patient’s susceptibility to dental abcesses, good oral hygiene along with regular dental examination is of paramount importance.

Antibody therapy is also a viable form of treatment of X linked hypophosphatemia. The Burosumab-twza injection makes use of monoclonal antibodies that bind to and inhibit the activity of excess fibroblast growth factor 23, thus restoring the balance of phosphate levels in the blood. It can be used in adults and children older than 6 months old. It is injected once in every 4 weeks for adults and once in every 2 weeks for children between the ages of 6 months and 17 years (American Dental Association).

Dental caries and attrition are also common symptoms of X linked hypophosphatemia. Bacterial invasion into the dental pulp through deformities of the enamel and dentin can also lead to pulpitis. The prevention of abcesses and oral issues can only be assured by early detection and treatment of the disorder. The use of polycarbonate crowns in deciduous teeth can prevent attrition and enamel defects. More invasive procedures such as dental implants are necessary if the disorder has gone undetected for a very long period of time leading to severe dental damage (NCBI).


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