Senior-Loken Syndrome

Related Terms

IQCB1 gene, juvenile nephronophthisis with Leber amaurosis, juvenile nephronophthisis with retinal dystrophy, Leber congenital amaurosis, Loken-Senior syndrome, NPHP1 gene, NPHP3 gene, NPHP4 gene, NPHP5 gene, renal dysplasia and retinal aplasia, renal dysplasia-blindness hereditary, renal-retinal dysplasia, renal-retinal syndrome, SLS, SLS1.

Background

Senior-Loken syndrome (SLS) is a rare genetic disorder that affects the kidneys and eyes. The main symptoms of SLS include nephronophthisis, a progressive deterioration of the kidneys, and retinal dystrophy, a loss of vision. SLS usually becomes apparent during the first year of life.
SLS is likely caused by several different types of mutations in several genes. The genes involved are NPHP1, NPHP3, NPHP4, and NPHP5, also known as IQCB1. There is limited information indicating the possibility of several types of SLS. One source suggests that SLS1 is associated with mutations in the nephronophthisis-1 gene (NPHP1), SLS3 with mutations in the NPHP3 gene, SLS4 with mutations in the NPHP4 gene, and SLS5 with mutations in the NPHP5 gene, also known as IQCB1.
The type of mutation determines the disease. The NPHP1 gene provides instructions for making the nephrocystin protein, whose function is currently unknown. This gene is defective in other disorders as well, including nephronophthisis and Joubert syndrome. The NPHP3 gene provides instructions for making a protein that interacts with the nephrocystin protein. The NPHP4 gene provides instructions for making the nephrocystin-4 protein, whose function is also currently unknown. The NPHP5 gene provides instructions for making the nephrocystin-5 protein.
SLS is inherited, or passed down from parents to children, as an autosomal recessive trait. This means that two copies of the defective gene must be inherited, one from each parent, for the disease to appear.
SLS is extremely rare, with about 150 cases reported in the scientific literature. The exact prevalence of this condition is not known. The disorder affects males and females in equal numbers.
There is no cure for SLS. Treatment aims to relieve symptoms and to prevent or manage complications. Medications, dialysis, or kidney transplantation may become necessary depending on the severity of the disease.

Signs and symptoms

General: Symptoms of Senior-Loken syndrome (SLS) typically become apparent during the first year of life. However, some individuals with the condition do not exhibit symptoms until later in life.
Eyes: People with SLS have gradual deterioration of the retina that eventually leads to visual impairment and blindness. At birth, people with SLS tend to have fewer rods, retinal cells that are responsible for vision in low light, and cones, which are responsible for vision in brighter light. One of the earliest signs of SLS may be the inability to see at low light levels. Other eye symptoms include nystagmus, or involuntary eye movements, and cataract, a clouding of the lens of the eye.
Kidneys: The type of kidney disease seen in SLS is called nephronophthisis, which refers to progressive loss of kidney function caused by chronic interstitial nephritis and uremia. Chronic interstitial nephritis describes a condition in which the spaces between the tissues in the kidney become inflamed and dysfunctional. This can cause extreme thirst, nausea, vomiting, weight loss, fatigue, anemia, and eventually kidney failure. Uremia, which literally means "urine in the blood," is marked by an increase in the amount of waste products in the blood that are not properly eliminated in the urine.
Other: Less frequent symptoms in people with SLS include hearing loss, diabetes, poor coordination, liver fibrosis (a buildup of connective tissue in the liver), short stature, and intellectual disability.

Diagnosis

General: To accurately diagnose Senior-Loken syndrome (SLS), a physical exam and thorough family history should be completed. During the patient interview, the clinician should ask probing questions about thirst, urinary frequency, fatigue, appetite, nausea, vomiting, and vision problems.
Eye exam: A thorough eye exam may identify problems with retinal cells, nystagmus (involuntary eye movements), and cataract (a clouding of the lens of the eye). An electroretinogram, which measures the electrical responses of different cells, can identify problems with the rod and cone cells of the retina.
Biopsy: In a biopsy, a small sample of tissue is removed from the body and analyzed in a lab. To diagnose SLS, a kidney biopsy may be done to look for changes in the kidney cells that indicate deteriorating function.
Laboratory tests: Laboratory tests that can help diagnose SLS include 24-hour urine collection, blood pressure measurements, blood urea nitrogen (BUN), a complete blood count, creatinine level, creatinine clearance, and urine specific gravity.
Imaging studies: Ultrasound, which uses sound waves to create a picture of an internal organ, can be used to help diagnose SLS. In particular, an ultrasound of the kidney can help identify problems with kidney structure and function.
Genetic testing: If SLS is suspected, a genetic test may be performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for the presence of a defect in the causative genes. If this defect is detected, a positive diagnosis is made.
Prenatal DNA testing: If there is a family history of SLS, prenatal testing may be performed to determine whether the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) can diagnose SLS. However, because there are serious risks associated with these tests, patients should discuss the potential health benefits and risks with a medical professional.
During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus, and a small amount of amniotic fluid is removed from the sac surrounding the fetus. Cells in the fluid are then analyzed for normal and abnormal chromosomes. This test is performed after 15 weeks of pregnancy. The risk of miscarriage is about one in 200-400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.
During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the placenta between the ninth and 14th weeks of pregnancy. CVS may be performed through the cervix or through the abdomen. The cells in the tissue sample are then analyzed for the causative mutations. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.

Complications

Kidney failure: Kidney disease is progressive in Senior-Loken syndrome (SLS), so kidney failure often develops. Kidney failure may be life threatening if not properly treated with dietary restriction and dialysis.
Visual impairment: Progressive damage to the optic nerve eventually causes severe visual impairment and blindness in people with SLS.

Treatment

General: There is no known cure for Senior-Loken syndrome (SLS). Treatment aims to reduce symptoms and prevent complications.
Dialysis: When the kidneys begin to fail, patients can undergo dialysis to restore the filtering function of the kidneys. In hemodialysis, a patient's blood is circulated into an external filter and cleaned. The filtered blood is then returned to the body. In peritoneal dialysis, a fluid containing dextrose is introduced into the abdomen through a tube. This solution absorbs the wastes in the body and is then removed.
Diet: Careful planning and monitoring of diet can help manage the progressive kidney disease seen in SLS. The diet should be adequate in calories and protein to ensure growth. There is some controversy about whether a protein-restricted diet can delay the progression of kidney disease. Individualized diet plans can be created with the help of a registered dietitian (RD).
Transplantation: Some patients who experience kidney failure may undergo kidney transplantation. However, transplantation is associated with complications, including infection and the possibility of organ rejection. To reduce the chance of rejection, patients may need to take immunosuppressive drugs.
Visual assistance: Eyeglasses may improve vision up to a point in people with SLS. Because almost all people with SLS progressively lose vision, they should be instructed early in life in the use of Braille, adaptive equipment, mobility aids, and computing skills specific for low vision. Various visual aids can be used to meet the individual needs of people with SLS. These may include large-print books and other reading materials, high-contrast written materials, hand-held monoculars, video enlargement machines, and other types of magnifiers. In addition, children and adults attending school may benefit from a printed copy of the teacher's board notes. People with SLS may also benefit from various specialized computer programs that address their individual needs.

Integrative therapies

Note: Currently, there is a lack of scientific evidence on the use of integrative therapies for the treatment or prevention of Senior-Loken syndrome (SLS). The therapies listed below have been studied for kidney disease, a complication of SLS. These integrative therapies should be used only under the supervision of a qualified healthcare provider and should not be used instead of other proven therapies.
Good scientific evidence:
Rhubarb: A traditional Chinese medicine, rhubarb has shown positive effects on kidney failure in the lab and seems promising in human studies. In some studies, rhubarb is more effective than captopril for chronic kidney failure, and rhubarb combined with captopril is more effective than either substance alone. Higher-quality studies are necessary to confirm this hypothesis.
Avoid if allergic or sensitive to rhubarb. Avoid using rhubarb for more than two consecutive weeks, because it may induce tolerance in the colon, melanosis coli, laxative dependence, pathological alterations to the colonic smooth muscles, and substantial loss of electrolytes. Avoid with gastric atony, colitis, Crohn's disease, dehydration with electrolyte depletion, diarrhea, hemorrhoids, insufficient liver function, intestinal obstruction or ileus, irritable bowel syndrome, menstruation, pre-eclampsia, renal disorders, ulcerative colitis, and urinary problems. Avoid handling rhubarb leaves, as they may cause contact dermatitis. Avoid rhubarb in children under age 12 because of the risk of water depletion. Use cautiously with bleeding disorders, cardiac conditions, anticoagulation therapy, constipation, a history of kidney stones, or thin or brittle bones. Use cautiously if taking antipsychotic drugs or oral drugs, herbs, or supplements, including calcium, iron, and zinc. Avoid if pregnant or breastfeeding.
Unclear or conflicting scientific evidence:
Acupuncture: The practice of acupuncture originated in China 5,000 years ago. Today it is widely used throughout the world and is one of the main pillars of Chinese medicine. There has been limited research on acupuncture for kidney disorders such as gouty renal damage. There is currently not enough evidence to recommend for or against acupuncture in these conditions.
Needles must be sterile in order to avoid disease transmission. Avoid with valvular heart disease, infections, bleeding disorders, neurological disorders, or medical conditions of unknown origin, or with anticoagulants (drugs that increase the risk of bleeding). Avoid on areas that have received radiation therapy. Use cautiously with pulmonary disease such as asthma or emphysema. Use cautiously in elderly or medically compromised patients, diabetics, or those with a history of seizures. Avoid electroacupuncture in patients with arrhythmia (irregular heartbeat) or pacemakers. Avoid during pregnancy.
Arabinogalactan: Arabinogalactans belong to a group of carbohydrates called polysaccharides. When consumed in the diet, arabinogalactan comes from the wood of the larch tree (Larix species) and is approved for use as a dietary fiber by the U.S. Food and Drug Administration (FDA). Although early results of arabinogalactan's effect in patients with chronic kidney failure are promising, more studies are needed.
Avoid if allergic or sensitive to arabinogalactan or larch. People who are exposed to arabinogalactan or larch dust may have irritation of the eyes, lungs, or skin. Use cautiously in people with diabetes, digestive problems, or immune system disorders, and in people who consume a diet that is high in fiber or low in galactose. Arabinogalactan should not be used during pregnancy or breastfeeding.
Astragalus: Astragalus products are derived from the roots of Astragalus membranaceus or related species native to China. In traditional Chinese medicine, astragalus is commonly found in mixtures with other herbs and is used in the treatment of numerous ailments, including heart, liver, and kidney diseases, as well as cancer, viral infections, and immune system disorders. Several animal and human studies report that kidney damage from toxins and kidney failure may be improved with the use of astragalus-containing herbal mixtures. Overall, this research has been poorly designed and reported. Astragalus alone has not been well evaluated. Better-quality research is necessary before a conclusion can be drawn.
Avoid if allergic to astragalus, peas, or any related plants, or with a history of Quillaja bark-induced asthma. Avoid with aspirin or aspirin products or herbs or supplements with similar effects. Avoid with inflammation or fever, stroke, transplant, or immune deficiencies such as HIV/AIDS. Stop use two weeks before surgery or dental or diagnostic procedures with a risk of bleeding, and avoid use immediately following these procedures. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders, or kidney disorders. Use cautiously with blood thinners, blood sugar drugs, diuretics, or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding.
Chitosan: Chitosan comes from chitin, which is part of the outer shell-like structure of insects, spiders, and crustaceans. Limited evidence suggests that chitosan may be useful during long-term hemodialysis. Further studies are needed to determine its safety and efficacy.
Avoid if allergic or sensitive to chitosan or shellfish. Use cautiously with diabetes or bleeding disorders. Use cautiously if taking drugs, herbs, or supplements that lower blood sugar or increase the risk of bleeding. Chitosan may decrease absorption of fat and fat-soluble vitamins from foods. Chitosan is not recommended during pregnancy or breastfeeding.
Coenzyme Q10: Coenzyme Q10 (CoQ10) is produced in the human body and is necessary for the basic functioning of cells. There are initial data to support the use of CoQ10 in the treatment of kidney failure. More research is needed before a recommendation can be made.
No reported allergy is associated with coenzyme Q10 supplements, although rash and itching have been reported rarely. Stop use two weeks before surgery or dental or diagnostic procedures with a bleeding risk, and do not use immediately following these procedures. Use caution with a history of blood clots, diabetes, high blood pressure, heart attack, or stroke, or with anticoagulants (blood thinners) or antiplatelet drugs, such as aspirin, warfarin, and clopidogrel (Plavix?), and with blood pressure, blood sugar, cholesterol, or thyroid drugs. Avoid if pregnant or breastfeeding.
Cordyceps: Cordyceps sinensis, the Cordyceps species most widely used as a dietary supplement, naturally grows on the back of caterpillar larvae of the moth Hepialus armoricanus Oberthur, found mainly in China, Nepal, and Tibet. In traditional Chinese medicine, cordyceps is used to strengthen kidney function. Two studies indicate that cordyceps may improve kidney function in patients with chronic kidney failure. More studies are needed to confirm these findings.
Avoid if allergic or hypersensitive to cordyceps, mold, or fungi. Use cautiously with diabetes, bleeding disorders, or prostate conditions; or if taking anticoagulant medications, immunosuppressive medications, hormone replacement therapy, or oral contraceptives. Avoid with myelogenous-type cancers. Avoid if pregnant or breastfeeding.
Soy: Soy and components of soy known as isoflavones have been studied scientifically for numerous health conditions. There is not enough evidence from human studies to recommend for or against the use of soy in the treatment of kidney diseases such as nephrotic syndrome. People with kidney disease should speak to their healthcare provider about recommended amounts of dietary protein and should bear in mind that soy is a high-protein food.
Avoid if allergic to soy. Breathing problems and rash may occur in sensitive people. Soy, as a part of the regular diet, is traditionally considered to be safe during pregnancy and breastfeeding, but there is limited scientific evidence. The effects of high doses of soy or soy isoflavones in humans are not clear, and therefore they are not recommended. There has been a case report of vitamin D deficiency rickets in an infant nursed with soybean milk, which is not specifically formulated for infants. People who experience colitis (intestinal irritation) from cow's milk may experience intestinal damage or diarrhea from soy. It is not known whether soy or soy isoflavones share the same side effects as estrogens, such as an increased risk of blood clots. The use of soy is often discouraged in patients with hormone-sensitive cancers, such as breast, ovarian, or uterine cancer. Other hormone-sensitive conditions such as endometriosis may also be worsened. Patients taking blood-thinning drugs such as warfarin should check with a doctor and pharmacist before taking soy supplementation.
Fair negative scientific evidence:
Arginine: It has been suggested that arginine may be a useful supplement in people diagnosed with kidney failure. However, results from available studies do not support this claim. A small randomized controlled clinical trial studied the ability of L-arginine to improve dilation of blood vessels in children with chronic renal failure. Results showed that blood vessel dilation was not improved with oral L-arginine, suggesting that dietary supplementation is not a beneficial or useful clinical approach in children with chronic renal failure.

Prevention

General: Because Senior-Loken syndrome (SLS) is an inherited condition, there is currently no known way to prevent the disease. However, a number of options are available for prospective parents with a family history of SLS.
Genetic testing and counseling: Individuals who have SLS may meet with genetic counselors to discuss the risks of having children with the disease. Individuals with a family history of SLS may meet with a genetic counselor to determine whether they carry a defective gene. Carriers can be determined through detailed family histories or genetic testing.
Known carriers of SLS may undergo genetic counseling before conceiving a child. Genetic counselors can explain the options and the associated risks of various tests, including preimplantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS).
Preimplantation genetic diagnosis (PGD) may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the defective gene (genes involved are NPHP1, NPHP3, NPHP4, and NPHP5, or IQCB1), and only the embryos that are not affected may be selected for implantation.
Because SLS can be detected in a developing fetus, parents may choose whether to continue the pregnancy. Genetic counselors may assist parents with these difficult decisions.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

American Kidney Fund, Inc. .
American Urological Association Foundation. .
Caridi G, Murer L, Bellantuono R, et al. Renal-retinal syndromes: association of retinal anomalies and recessive nephronophthisis in patients with homozygous deletion of the NPH1 locus. Am. J. Kidney Dis. 32: 1059-62, 1998.
Clarke MP, Sullivan TJ, Francis C, et al. Senior-Loken syndrome: case report of two siblings and association with sensorineural deafness. Brit. J. Ophthal. 76: 171-2, 1992.
Dekaban AS. Familial occurrence of congenital retinal blindness and developmental retinal lesions. J. Genet. Hum. 17: 289-96, 1969.
National Kidney Foundation. .
Natural Standard: The Authority on Integrative Medicine. .
National Eye Institute. .
Omran H, Sasmaz G, Haffner K, et al. Identification of a gene locus for Senior-Loken syndrome in the region of the nephronophthisis type 3 gene. J. Am. Soc. Nephrol. 13: 75-9, 2002.
Scheuermann MJ, Otto E, Becker A, et al. Mapping of gene loci for nephronophthisis type 4 and Senior-Loken syndrome to chromosome 1p36. Am J Hum Genet. 2002;70:1240-6.
Warady BA, Cibis G, Alon U, et al. Senior-Loken syndrome: revisited. Pediatrics 94: 111-2, 1994.

Causes

Genetic mutations: Senior-Loken syndrome (SLS) is likely caused by several different types of mutations, or defects, in several genes. The genes involved are NPHP1, NPHP3, NPHP4, and NPHP5, also known as IQCB1.
Autosomal recessive inheritance: SLS is inherited as an autosomal recessive trait, meaning that a person must inherit two copies of the defective gene, one from each parent, for the disease to appear. Individuals who inherit only one copy of the defective gene generally have no symptoms and are called carriers, because they can pass on the disorder to their children.
Random occurrence: It is not known whether SLS can occur in individuals with no family history of the disorder.

Risk factors

Because Senior-Loken syndrome (SLS) is inherited, the only known risk factor is a family history of the condition. SLS is inherited as an autosomal recessive trait, meaning that a person must inherit two copies of the defective gene, one from each parent, for the disease to appear. Individuals who inherit only one copy of the defective gene generally have no symptoms and are called carriers, because they can pass on the disorder to their children.
If one parent is a carrier, then each child will have a 50% chance of inheriting one defective gene and also being a carrier. If both parents are carriers, each child has a 25% chance of inheriting two defective genes, a 50% chance of inheriting only one defective gene, and a 25% chance of inheriting neither defective gene. Therefore, if both parents are carriers, about one out of four children will have SLS.

Types of the disease

There is limited information indicating the possibility of several types of Senior-Loken syndrome (SLS). One source suggests that SLS1 is associated with a mutation in the nephronophthisis-1 gene (NPHP1), SLS3 with a mutation in the NPHP3 gene, SLS4 with a mutation in the NPHP4 gene, and SLS5 with a mutation in the NPHP5 (IQCB1) gene. If different forms of the disease do exist, they appear to all have similar symptoms and differ only in the gene that is affected.