Løken-Senior Syndrome is a rare disorder inherited as an autosomal recessive genetic trait. This disorder is characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life.
Løken-Senior Syndrome is a rare inherited disorder characterized by progressive kidney and eye problems.
The nephronophthisis with or without medullary cystic renal disease appears in the first year of life. The kidney problems are present at birth in some families, but develop very gradually and take a long time before symptoms become apparent in other families. Progressive failure of kidney function occurs as a result of degeneration or loss of function of the small collecting tubes (tubules) in the kidney. This can cause uremia and chronic interstitial nephritis.
Chronic interstitial nephritis is a kidney syndrome in which the spaces between the tissue of the kidney (interstitial) become inflamed and structural changes occur. Eventually the patient may have symptoms such as nausea, vomiting, weight loss, fatigue, anemia and ultimately kidney failure.
Uremia is a condition that is characterized by a gradual increase of urea and other by-products of protein breakdown in the blood, causing a severe toxic condition. Normally, these by-products of protein breakdown would be passed in the urine.
The progressive atrophy of the retina of the eye may be like Leber’s Amaurosis with an absence of light gathering cells (cones and rods) of the retina at birth. A decrease in visual responsiveness at birth is the first sign of this disorder with roving eye movements (nystagmus) being apparent in the first two months of life.
In other cases of Løken-Senior Syndrome the progressive atrophy of the retina of the eye may take a course similar to Retinitis Pigmentosa. This condition typically becomes apparent later in life with the earliest symptom being difficulty seeing in dimly lit places (night blindness). This is slowly followed by tunnel vision. The rate of progression can vary.
Other symptoms have been noted in particular families such as diabetes insipidus, neurosensory hearing loss, muscular incoordination caused by disease of the cerebellum in the brain (cerebellar ataxia), abnormal formation of fibrous tissue in the liver (hepatic fibrosis) and skeletal abnormalities.
Løken-Senior Syndrome is inherited as an autosomal recessive trait. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
The variability between families affected by Løken-Senior syndrome may be explained by different gene mutations in more than one gene (genetic heterogeneity). Several different gene abnormalities have been noted in individuals with Løken-Senior syndrome including a deletion of both copies of one of the genes for nephronophthisis (NPHP1), an abnormal gene near the NPHP3 locus on chromosome 3 and an abnormal gene overlapping the NPHP4 locus on chromosome 1.
Løken-Senior Syndrome is a very rare disorder affects males and females in equal numbers. There have been over one hundred and fifty cases of this disorder reported in the medical literature.
Patients with Medullary Cystic Disease need careful management of uremia when it occurs. Diet must be carefully monitored. An increase of calories in the diet should be coupled with a reduction in the total content of dietary protein. Sufficient carbohydrates and fats should be consumed to provide energy and prevent the body from metabolizing its own proteins.
Kidney failure may need to be managed with hemodialysis. Kidney transplantation is sometimes indicated.
When the retinal atrophy in Løken-Senior Syndrome resembles Retinitis Pigmentosa, the patient may benefit from various visual aids. The aids may be 1) optical aids, such as Corning and NOIR glasses, the Fresnel Prising telescopes, microscopes and night vision aids; 2)non-optical aids, such as the Wide Angle Mobility Light, paper guides, large print typewriters and adjustable stands; and 3) electronic aids such as Apollo Laser and Visualtek closed-circuit TV, reading machines and talking computers.
Genetic counseling may be of benefit for patients and their families.
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McKusick,VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 266900: Last Edit Date; 12/26/2002.