X-Linked Hypophosphataemic Rickets or X-linked Hypophosphataemia (XLH)
XLH is a rare genetic disorder of phosphate metabolism, affecting approximately 1 in 20,000 people. Phosphate is lost in the urine and its levels in the blood are very low, leading to soft and weak bones (rickets in children, osteomalacia in adults). It is caused by mutation in the PHEX gene, which is carried from one generation to the other (located on X-chromosome). Only one parent needs to carry the mutation to be passed to a child (X-linked dominant inheritance). A female with XLH has a 50% chance of passing XLH to each of her children. A male with XLH will pass XLH to all of his daughters, but to none of his sons. In some cases, XLH is diagnosed in families with no previous history of the disorder.
Symptoms of XLH in children vary and may include: bow legs or knock-knees, abnormal skull shape, waddling gait, pain in the muscles or bones, weakness and short stature. Also, presence of tooth abscesses is relatively common. In adults with the disorder, pain and stiffness of joints and tendons is a common feature, especially at the ankles, knees, hips and spine. Hearing loss is also possible.
XLH is diagnosed based on a physical exam, blood tests, X-rays, and family history. There is X-ray evidence of rickets (“soft bones”), low phosphorus in the blood with high excretion in the urine, elevated alkaline phosphatase, normal calcium and vitamin D levels and normal or mildly elevated parathormone.
Life-long monitoring of bone disease, renal function and dental health is essential. In children, treatment is usually started at the time of diagnosis and continues until bones stop growing. Most patients are managed with phosphate supplements and active vitamin D (a-calcidol or calcitriol). Some of them may require growth hormone, corrective surgery and dental treatment. For adults, the main treatment goal is to improve pain. New treatment is emerging (burosumab, approved in April 2018), targeting FGF-23, a protein that plays a key-role in handling phosphorus in the body.The long-term outcome varies, depending on severity and complications.