$Unique_ID{BRK04189} $Pretitle{} $Title{Rickets, Hypophosphatemic} $Subject{Rickets, Hypophosphatemic Familial Hypophosphatemic (Vitamin D-Resistant) Rickets X-Linked Hypophosphatemia X-Linked Vitamin D-Resistant Rickets Hypophosphatemic D-Resistant Rickets I HPDR I Hereditary Type II Hypophosphatemia Hypophosphatemic D-Resistant Rickets II HPDR II Phosphate Diabetes Rickets Pseudovitamin D Deficiency Rickets (Vitamin D-Dependent Rickets, Type I) Osteomalacia Fanconi's Syndrome } $Volume{} $Log{} Copyright (C) 1987, 1988, 1989, 1992 National Organization for Rare Disorders, Inc. 417: Rickets, Hypophosphatemic ** IMPORTANT ** It is possible the main title of the article (Hypophosphatemic Rickets) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names, disorder subdivisions, and related disorders covered by this article. Synonyms Familial Hypophosphatemic (Vitamin D-Resistant) Rickets X-Linked Hypophosphatemia X-Linked Vitamin D-Resistant Rickets Hypophosphatemic D-Resistant Rickets I HPDR I Hereditary Type II Hypophosphatemia Hypophosphatemic D-Resistant Rickets II HPDR II Phosphate Diabetes Information on the following diseases can be found in the Related Disorders section of this report: Rickets Pseudovitamin D Deficiency Rickets (Vitamin D-Dependent Rickets, Type I) Osteomalacia Fanconi's Syndrome General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Hypophosphatemic Rickets is a rare genetic form of Rickets characterized by impaired transport of phosphate and diminished Vitamin-D metabolism in the kidneys. Additionally, calcium and phosphate are not absorbed properly in the intestines which can lead to softening of bones. Major symptoms include skeletal changes, weakness and slowed growth. Cases affecting females are usually less severe than those affecting males. One rare acquired form of this disorder may be associated with a benign tumor. Symptoms Symptoms of Hypophosphatemic Rickets are usually first noticed after eighteen months of age. Dental problems may develop such as decay and abscesses or late eruption of teeth. Abnormalities may include softening or thinning of bones, fractures, and/or abnormal bony extensions at the site of muscular attachments. Symptoms such as weakness, intermittent muscle cramps, a "waddling" walk due to abnormalities in the hip joint, pain in the knees, knock knees or bow legs, diminished growth (especially of the legs), and abnormal skull or rib development may also occur. Cases of Hypophosphatemic Rickets may range from mild to severe. Some cases may have no noticeable symptoms while others may be marked by pain and/or stiffness of the back, hips and shoulders possibly limiting mobility. In very rare cases, some hair loss may occur. Causes Hypophosphatemic Rickets is inherited as a dominant X-linked trait. Symptoms are caused by altered metabolism of phosphorus, calcium, and Vitamin-D although the exact mechanism through which this occurs is not well understood. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In X-linked dominant disorders the female with only one X chromosome affected will develop the disease. However the affected male always has a more severe condition. Sometimes affected males die before birth so that only female patients survive.) Affected Population Hypophosphatemic Rickets may affect males and females in equal numbers, although cases affecting males are usually more severe than those affecting females. Related Disorders Several forms of Rickets exist, all of which are characterized primarily by weakening of bones due to abnormal calcium metabolism as well as possible decreases of other substances in the body. Rickets may be either acquired or inherited. Asymptomatic hypophosphatemic adult carriers are almost always females. Symptoms of the following disorders can be similar to Hypophosphatemic Rickets. Comparisons may be useful for a differential diagnosis: Rickets is due to a vitamin-D deficiency resulting in deficient calcification of tissue which normally hardens into bone. This condition can begin at any time of life and may be successfully treated with large doses of vitamin-D. Pseudovitamin D Deficiency Rickets (Vitamin D-Dependent Rickets, Type I) is characterized by more severe skeletal changes and weakness than those of Hypophosphatemic Rickets. This disorder is caused by abnormal vitamin D metabolism and is inherited as an autosomal recessive trait. This type of rickets often begins earlier than Hypophosphatemic Rickets. Blood levels of calcium are severely diminished in patients Vitamin-D Dependent Rickets, although phosphate levels appear normal or only slightly deficient. Amino acids become lost in the urine due to a kidney dysfunction. Intermittent muscle cramps may occur. Convulsions and abnormalities of the spine and pelvis may also develop. Osteomalacia is a disorder characterized by a gradual softening and bending of the bones. Pain may occur in various degrees of severity. Softening occurs because solid bones have failed to form properly (calcify) due to lack of Vitamin-D or a kidney dysfunction. This illness is more common in women than in men, and often begins during pregnancy. It can exist alone or in association with other disorders, such as Hypophosphatemic Rickets. Fanconi's Syndrome is characterized by kidney dysfunction and bone abnormalities similar to those of Hypophosphatemic Rickets. Excess amounts of phosphate, amino acids (usually bicarbonate), glucose, and uric acid are eliminated in the urine. This rare disorder is thought to be inherited through a recessive gene. Bone symptoms include rickets in children and softening of bones (osteomalacia) in adults. Fanconi's Syndrome may be associated with a variety of inherited metabolic disorders such as cystinosis, Lowe's Syndrome, a form of Tyrosinemia, hereditary fructose intolerance, Wilson's Disease, Galactosemia, and a glycogen storage disorder. For more information on the above disorders, choose the following words as your search terms in the Rare Disease Database: Fanconi, Lowe, fructose intolerance, cystinosis, Wilson, galactosemia, and glycogen storage. Therapies: Standard Treatment of Hypophosphatemic Rickets consists of increasing phosphate levels as well as vitamin-D. The dosage of vitamin-D is gradually increased until bone healing occurs. This treatment must be carefully monitored to prevent loss of calcium. Vitamin-D alone decreases loss of phosphate through the kidney but does not influence the patient's growth pattern, the level of phosphate absorbed in the intestines, nor the kidney dysfunction. Phosphate alone may improve absorption of calcium and phosphate in the intestines as well as enhance bone healing, but it may not sustain these improvements unless vitamin-D is also prescribed. Recent evidence suggests that long-term calcium plus phosphate supplements may result in better bone mineralization than occurs with vitamin-D plus phosphate therapy. Covering teeth with chrome crowns may be successful in preventing spontaneous abscesses. Genetic counseling may be of benefit for patients and their families. Those rare cases which are caused by tumors rather than heredity can be treated through surgical removal of the tumor. Therapies: Investigational Bone growth abnormalities associated with Hypophosphatemic Rickets can be surgically removed in an attempt to prevent further shortening or deformities of affected arms or legs. More research is necessary before this procedure can be recommended for all but the most severe cases of Hypophosphatemic Rickets. In a study carried out by scientists in Australian children with X-Linked Hypophsatemic Rickets using the enzyme calcitriol (1x, 25 dihydroxyvitamin D3) and phosphate, a slight increase in height was noted along with the development of calcium deposits in the kidneys (nephrocalcinosis). These scientists recommend conservative use of calcitriol nd careful observation of patients to guard against serious kidney damage. Treatment should be discontinued when growth has stopped. This disease entry is based upon medical information available through February 1992. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Hypophosphatemic Rickets, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References PROPHYLACTIC DENTAL TREATMENT FOR A PATIENT WITH VITAMIN D-RESISTANT RICKETS: REPORT OF CASE: G. H. Breen; Asdc J Dent Child (Jan.-Feb. 1986, issue 53(1)). Pp. 38-43. EARLY DIAGNOSIS AND EARLY TREATMENT OF HYPOPHOSPHATEMIC VITAMIN D- RESISTANT RICKETS: E. Schaumberger, et al.; Klin Padiatr (Jan.-Feb. 1986, issue 198(1)). Pp. 44-48. TIBIAL BOWING EXACERBATED BY PARTIAL PREMATURE EPIPHYSEAL CLOSURE IN SEX- LINKED HYPOPHOSPHATEMIC RICKETS: W.H. McAlister, et al.; Radiology (February 1987, issue 162(2)). Pp. 461-463.