$Unique_ID{BRK03945} $Pretitle{} $Title{Lowe's Syndrome} $Subject{Lowe's Syndrome Lowe's Disease Oculocerebrorenal Dystrophy Cerebro-Oculorenal Dystrophy Lowe-Bickel Syndrome Lowe-Terry-Mclachlan Syndrome Fanconi II Syndrome Cystinuria Glaucoma Cataracts Vitamin D Resistant Rickets} $Volume{} $Log{} Copyright (C) 1986, 1987, 1989, 1990, 1992, 1993 National Organization for Rare Disorders, Inc. 109: Lowe's Syndrome ** IMPORTANT ** It is possible that the main title of the article (Lowe's Syndrome) is not the name you expected. Please check the SYNONYM listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Lowe's Disease Oculocerebrorenal Dystrophy Cerebro-Oculorenal Dystrophy Lowe-Bickel Syndrome Lowe-Terry-Mclachlan Syndrome Information on the following diseases can be found in the Related Disorders section of this report: Fanconi II Syndrome Cystinuria Glaucoma Cataracts Vitamin D Resistant Rickets 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. Lowe's Syndrome is a rare inherited, metabolic disorder characterized by eye abnormalities such as congenital cataracts and glaucoma, bone malformations caused by Vitamin D resistant rickets, mental retardation and impairment of kidney function. Symptoms The symptoms of Lowe's Syndrome become apparent in early infancy. It affects only males (of all races), but is most common in those with fair coloring. The muscles may be flabby, the joints unusually flexible (hypermobility) and there may be little or no muscle reflexes (areflexia). Other symptoms of Lowe's Syndrome may include bowed legs (rickets), underdeveloped testes, a distention of the eyeballs due to fluid buildup (hydropthalmos), cataracts and glaucoma during infancy, a vertical fold on either side of the nose and between the eyelids (epicanthal folds), excess fatty tissue, wide ranging weight and temperature fluctuations, excessive activity level (hyperactivity), and mental retardation. There may be a high level of amino acids (aminoaciduria) and phosphates (phosphaturia) in the urine, a low level of ammonia, and an impairment of kidney function (tubular acidosis). The blood may be slightly acidic, and have elevated nitrogen levels and electrolyte abnormalities. Microscopic studies may show abnormalities in the kidneys, testes, eye and brain. Female carriers, who have a single gene for the disorder, sometimes have opacities in the lens of the eye. Causes Lowe's Syndrome is a metabolic disorder transmitted through X-linked recessive genes. Scientists believe they have located the gene responsible for the disease. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. X-linked recessive disorders are conditions which are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a fifty percent risk of transmitting the carrier condition to their daughters, and a fifty percent risk of transmitting the disease to their sons. In 1992 researchers located the gene on the X chromosome that causes Lowe's Syndrome. Prenatal diagnosis of Lowe's Syndrome may be possible with the discovery of the gene that causes the syndrome as well as a test to determine who is a carrier of the disease gene. Affected Population Lowe's Syndrome is very rare and affects only males. It is usually recognized in early infancy. Related Disorders Symptoms of the following disorders can be similar to those of Lowe's Syndrome. Comparisons may be useful for a differential diagnosis: Fanconi II Syndrome usually accompanies some other inherited disease, most commonly the inherited metabolic disease, cystinosis. It is characterized by abnormal renal proximal tubular function, particularly in the reabsorption of glucose, phosphates, amino acids, bicarbonate, uric acid, water, potassium and sodium. This form of Fanconi's Syndrome may result from drug toxicity, kidney transplantation, multiple myeloma and other malignancies, amyloidosis, certain other hereditary amino acid syndromes, and certain toxins. (For more information on this disorder, choose "Cystinosis" as your search term in the Rare Disease Database). Cystinuria is an inherited disorder characterized by abnormal intestinal and kidney transport of the dibasic amino acids cystine, lysine, and arginine. This results in excessive amounts of cystine stones in the kidney and urinary tract. Cystinuria is the most common of a group of disorders involving abnormal amino acid transport. (For more information on this disorder, choose "Cystinuria" as your search term in the Rare Disease Database). The following conditions can be associated with Lowe's Syndrome: Glaucoma is a disease of the eye characterized by increased intraocular pressure which results in changes to the optic nerve and may cause blindness. This disorder tends to occur in older people and is prevalent in the elderly. Cataracts are abnormalities in the lens of the eye which causes a loss of transparency (opacity). They can occur in either one or both eyes, and are quite common in the elderly. Congenital cataracts affect babies or young children and are considered to be a rare birth defect. Cataracts tend to cause cloudy vision, and in many cases may result in blindness when left untreated. Vitamin D Resistant Rickets is a condition caused by abnormal Vitamin D metabolism and lower than normal calcium in the blood. It occurs most often in infancy and early childhood and is characterized by a bending and distortion of the bones, a delayed closing of the fontanels of the head, pain in the muscles and excessive sweating. (For more information on this disorder, choose "Vitamin D Resistant Rickets" in the Rare Disease Database.) Therapies: Standard Treatment of Lowe's Syndrome consists of appropriate medications necessary to reduce or alleviate symptoms and to correct the behavioral and kidney (renal) problems. The low level of phosphorus in the blood of males with Lowe's Syndrome is treated with oral replacement of phosphorus alone, or phosphorus in combination with Vitamin D to prevent the onset of rickets. To prevent the onset of acidosis (accumulation of acid in the blood and bloody tissues), an alkaline solution is often prescribed. Surgery or drugs may be considered for treatment of eye problems such as cataracts and glaucoma; cataracts can be removed in infancy. Boys with this disorder may need to wear eyeglasses or contact lenses. In some cases, prenatal diagnosis may be possible. Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive. Therapies: Investigational At the present time, studies are being conducted on the effectiveness of the drugs carnitine and thyrocalcitonin as possible treatments of Lowe's Syndrome. More research must be conducted to determine long-term safety and effectiveness of these drugs as a treatment for this disorder. Researchers at Cullen Eye Institute of the Baylor College of Medicine in Houston, Texas are studying inherited retinal diseases including Lowe's Syndrome. Families with at least two affected members and both parents living are needed to participate in this program. Other disorders included in the study are Leber's Congenital Amaurosis, Usher Syndrome (Types I and II), Macular Degeneration and Polymorphic Macular Degeneration, Lawrence-Moon-Biedl Syndrome, Rod Monochromacy (Complete Congenital Achromatopsia), Blue Cone Monochromacy (Congenital Incomplete X-linked Achromatopsia), Choroidermia, Hereditary X-linked cataracts, and other hereditary diseases with significant visual impact. Another important investigation on Lowe's Syndrome is currently underway at the National Institutes of Child Health and Human Development (NICHD) Health under the direction of Lawrence Charnas, M.D., NIH/National Institute of Child Health and Human Development, Bldg. 10, Rm. 8C-429, Bethesda, MD, 20892, (301) 496-6683). Current research strongly suggests that the Lowe's Syndrome gene controls production of a specific enzyme, inositol-polyphosphate-5-phosphatase. This enzyme discovery will open the door to further investigations into the metabolic defect and how it relates to various medical problems. This disease entry is based upon medical information available through April 1993. 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 Lowe's Syndrome, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Lowe's Syndrome Association 222 Lincoln Street West Lafayette, IN 47806 (317) 743-3634 NIH/National Institute of Child Health and Human Development (NICHD) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5133 For Genetic Information 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 ORAL CARNITINE THERAPY IN CHILDREN WITH CYSTINOSIS AND RENAL FANCONI SYNDROME. w. Gahl et al.; J CLIN INVEST (February 1988, issue 81 (2)). Pp. 549-560. EFFECT OF THYROCALCITONIN ON RENAL REABSORPTION OF BICARBONATE. BIOMEDICINE (December 1979, issue 31 (8)). Pp. 230-233. THE OCULOCEREBRAL SYNDROME OF LOWE, Charnas, L. and Gahl, W; National Institutes of Health Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 1991. CLINICAL LABORATORY FINDINGS IN THE OCULOCEREBRAL SYNDROME OF LOWE, WITH SPECIAL REFERENCE TO GROWTH AND RENAL FUNCTION, Charnas, L., et al.; N Eng J Med, May 9, 1991, (issue 324). Pp. 1318-1325.