The clinical signs of XLH are quite variable.
Major symptoms of XLH include skeletal malformations, bone pain, abnormally
bowed legs (see below), and generalized, but usually mild muscle weakness.
Affected infants may experience failure to thrive resulting in low weight
and a short, stocky stature (with an adult height of usually less than 165
cm). However, most often the symptoms appear at the age of 12 to 18 months
and affected infants show a waddling gait, bowing of the legs with coxa
vara, genua vara or genus valga (all secondary to the weight-bearing
function). Dolichocephaly, Arnold-Chiari Syndrome, and
sensorineural hearing loss because of malformation of the inner ear have been
reported. Although serum phosphate levels are equally decreased in affected
males and females, the degree of bone involvement in males is significantly
more severe. Tetany, rachitic rosary, pectus deformity, and severe myopathy
are usually not features found in these patients. Beside bowing of the long
bones (especially of the lower extremities), radiographic features include
rachitic changes such as widening, fraying, and cupping of the growth plates
(particularly of the tibia, distal femur, radius, and ulna) and overall mild
osteopenia. Later on in life, signs of osteoarthritis in the knees and
ankles are common and coarsening of the trabecular pattern (consistent with
osteomalacia) in combination with Looser transformation zones can be
detected and may be associated with fractures and pseudofractures (more
common in adults). Dental problems such as cavities because of
hypomineralization of the enamel, primary teeth abscesses, but also enlarged
pulp chambers and a defect in the calcification of the dentin matrix (called
intraglobular dentin) are common findings in these patients. Enthesopathy
(the calcification of ligaments, tendons, joint capsules) is common after
the age of 40 years and is not only often responsible for the pain, but may
also limit joint mobility. Most often this affects elbows, shoulders, hips,
(fusion of the sacroiliac joints) or the spine (spinal hyperostosis), where
it may result in spinal canal stenosis, scoliosis, and significant
disability. Successful treatment consists of oral phosphate supplements
along with calcitriol (the active form of vitamin D) to avoid secondary
hyperparathyroidism as a consequence of the oral phosphate load. This
therapy requires a high compliance from the patient and his/her caregiver,
since this means not only taking the medications every 6 hours for many
years, but also frequent monitoring. However, phosphate and calcitriol
treatment increases the risk of nephrocalcinosis (the risk seems to be
correlated with the dose of phosphate administrated) and vitamin D toxicity.
Once treatment has been established, growth acceleration and correction of
the deformities (to a certain degree) have been described in many patients
(with a higher response rate in female patients).