Question: What is (are) Hypophosphatemic rickets ?
Answer: Hypophosphatemic rickets (previously called vitamin D-resistant rickets) is a disorder in which the bones become painfully soft and bend easily, due to low levels of phosphate in the blood. Symptoms usually begin in early childhood and can range in severity. Severe forms may cause bowing of the legs and other bone deformities; bone pain; joint pain; poor bone growth; and short stature. In some affected babies, the space between the skull bones closes too soon (craniosynostosis). This sometimes results in developmental abnormalities. Hypophosphatemic rickets is almost always inherited and may be caused by changes (mutations) in any of several genes. Most commonly it is due to the PHEX gene and inherited in an X-linked dominant manner. Less commonly it is inherited in an X-linked recessive manner (often called Dent disease); autosomal dominant manner; or autosomal recessive manner. Treatment involves taking phosphate and calcitriol in order to raise phosphate levels in the blood and promote normal bone formation.
Source: GARD

Question: What are the symptoms of Hypophosphatemic rickets ?
Answer: What are the signs and symptoms of Hypophosphatemic rickets? The symptoms of hypophosphatemic rickets usually begin in infancy or early childhood. Specific symptoms and severity can vary greatly among affected children. The condition can be so mild that there are no noticeable symptoms, or so severe that it causes bowing of the legs and other bone deformities; bone pain; joint pain; and short stature. Other symptoms may include premature closure of the skull bones in babies (craniosynostosis); limited joint movement; and dental abnormalities. If left untreated, symptoms worsen over time. The Human Phenotype Ontology provides the following list of signs and symptoms for Hypophosphatemic rickets. If the information is available, the table below includes how often the symptom is seen in people with this condition. You can use the MedlinePlus Medical Dictionary to look up the definitions for these medical terms. Signs and Symptoms Approximate number of patients (when available) Abnormality of dental enamel 90% Abnormality of the metaphyses 90% Bone pain 90% Genu varum 90% Premature loss of teeth 90% Craniofacial hyperostosis 50% Enthesitis 50% Osteoarthritis 50% Short stature 50% Hearing impairment 7.5% Recurrent fractures 7.5% Abnormality of pelvic girdle bone morphology - Arthralgia - Bowing of the legs - Elevated alkaline phosphatase - Elevated circulating parathyroid hormone (PTH) level - Femoral bowing - Fibular bowing - Flattening of the talar dome - Frontal bossing - Hypomineralization of enamel - Hypophosphatemia - Hypophosphatemic rickets - Metaphyseal irregularity - Osteomalacia - Phenotypic variability - Renal phosphate wasting - Renal tubular dysfunction - Shortening of the talar neck - Spinal canal stenosis - Spinal cord compression - Tibial bowing - Trapezoidal distal femoral condyles - X-linked dominant inheritance - The Human Phenotype Ontology (HPO) has collected information on how often a sign or symptom occurs in a condition. Much of this information comes from Orphanet, a European rare disease database. The frequency of a sign or symptom is usually listed as a rough estimate of the percentage of patients who have that feature. The frequency may also be listed as a fraction. The first number of the fraction is how many people had the symptom, and the second number is the total number of people who were examined in one study. For example, a frequency of 25/25 means that in a study of 25 people all patients were found to have that symptom. Because these frequencies are based on a specific study, the fractions may be different if another group of patients are examined. Sometimes, no information on frequency is available. In these cases, the sign or symptom may be rare or common.
Source: GARD

Question: What causes Hypophosphatemic rickets ?
Answer: What causes hypophosphatemic rickets? Hypophosphatemic rickets is almost always hereditary and may be caused by mutations in any of several genes. The specific gene involved determines the way it is inherited. Most commonly, it is caused by a mutation in the PHEX gene. Other genes that can be responsible for the condition include the CLCN5, DMP1, ENPP1, FGF23, and SLC34A3 genes. The genes associated with hereditary hypophosphatemic rickets are involved in keeping a proper balance of phosphate in the body. Many of these genes directly or indirectly regulate a protein that normally inhibits the kidneys' ability to reabsorb phosphate into the blood. Mutations affecting the function of these genes increase the production (or reduce the breakdown) of the protein, causing the protein to be overactive. The overactivity of the protein reduces phosphate reabsorption by the kidneys, leading to the features of the condition. Rarer, sporadic, acquired cases are sometimes associated with benign (non-cancerous) mesenchymal tumors that decrease resorption of phosphate.
Source: GARD

Question: Is Hypophosphatemic rickets inherited ?
Answer: How is hypophosphatemic rickets inherited? Hypophosphatemic rickets is most often inherited in an X-linked dominant manner. This means that the gene responsible for the condition is located on the X chromosome, and having only one mutated copy of the gene is enough to cause the condition. Because males have only one X chromosome (and one Y chromosome) and females have two X chromosomes, X-linked dominant conditions affect males and females differently. Both males and females can have an X-linked dominant condition. However, because males don't have a second, working copy of the gene (as females do), they usually have more severe disease than females. If a father has the mutated X-linked gene: all of his daughters will inherit the mutated gene (they will all receive his X chromosome) none of his sons will inherit the mutated gene (they only inherit his Y chromosome) If a mother has the mutated X-linked gene, each of her children (both male and female) has a 50% chance to inherit the mutated gene. Less commonly, hypophosphatemic rickets is inherited in an X-linked recessive, autosomal dominant, or autosomal recessive manner.
Source: GARD