Nephronophthisis has an insidious onset and results from mutations in the NPHP genes. The ensuing tubulointerstitial nephritis can induce acute or chronic renal insufficiency and subsequently progress to end-stage kidney disease before the age of 20. Most patients present when the renal failure is in an advanced stage .
Depending on the onset of end-stage kidney disease, nephronophthisis has been divided into three clinical variants: infantile, juvenile, and adolescent .
The earliest symptoms are mild and can manifest in infancy or childhood as polyuria, polydipsia, secondary enuresis due to an impaired concentrating ability, and anemia. Additional features that may be observed include neurological disorders, liver fibrosis, and obesity.
Retinitis pigmentosa initially presents as night blindness (nyctalopia) slowly progressing to a considerable loss of peripheral visual field (tunnel vision) and finally to a complete absence of light perception. Cone function and central visual acuity are maintained until a late stage of the disease. A number of other ocular manifestations have been observed in Senior Loken syndrome including keratoconus, cataract, retinitis punctata albescens, and Coat's disease .
Entire Body System
- Refractory Anemia
Congenital medullary cystic disease of the kidney with severe refractory anemia. Am J Dis Child 1945; 69: 369–377. Google Scholar 2. Fanconi G, Hanhart E, von Albertini A, Euhlinger R, Dolivo G, Prader A. Die familiäre juvenile Nephronophthise. [link.springer.com]
Congenital medullary cysts of the kidneys with severe refractory anemia. Am. J. Dis. Child. 69, 369–377 (1945). 2 Fanconi, G., Hanhart, E. & Albertini, A. Die familiäre juvenile Nephronophthise. Hel. Pediatr. Acta 6, 1–49 (1951). 3 Hildebrandt, F. [doi.org]
Congenital medullary cysts of the kidneys with severe refractory anemia. Am. J. Dis. Child. 69, 369–377 (1945). 2. Fanconi, G., Hanhart, E. & Albertini, A. Die familiäre juvenile Nephronophthise. Hel. Pediatr. Acta 6, 1–49 (1951). 3. Hildebrandt, F. [nature.com]
FISH Probe Protocols Protocol, Procedure, or Form Name Last Modified Download Scientific Citations There are currently no FISH related citations for this gene. [empiregenomics.com]
- Failure to Thrive
Common findings include a failure to thrive and weakness. Anorexia, nausea, pruritus, bone pain, and neurologic symptoms herald ESRD. Because of salt wasting, hypertension is rare, except in the infantile form of nephronophthisis. [emedicine.medscape.com]
[…] to thrive Microphthalmia Oxycephaly Craniosynostosis Meningocele Abnormal retinal morphology Esotropia Glycosuria Renal cortical cysts Wide anterior fontanel Hypoplasia of the brainstem Trigonocephaly Dilatation Cryptorchidism Short neck Agenesis of [mendelian.co]
Failure to thrive (Infantile dermatitis) 138. Leopard syndrome • L Lentigenes • E Ecg abnormalities - Bundle Branch Block 7. [de.slideshare.net]
- Abdominal Tenderness
He had abdominal tenderness without guarding. Investigations revealed a lipase level of 3856 I U/l and an abdominal CT scan showed features of acute pancreatitis. [ncbi.nlm.nih.gov]
- Retinal Lesion
Ocular manifestations There are variable retinal lesions in Senior Loken syndrome, from Leber congenital amaurosis to retinitis pigmentosa. [symptoma.com]
Retinal lesions are variable, ranging from severe Leber congenital amaurosis ( LCA ), which can cause blindness in early infancy, to later onset retinitis pigmentosa (RP). Other ocular symptoms can include cataract, Coat’s disease, and keratoconus. [invitae.com]
- Progressive Loss of Vision
Unlike Usher Syndrome, where a progressive loss of vision is typical, vision loss in individuals with LCA usually remains stable through young adult life. Progression of vision loss later in life has not yet been clearly defined. [tsbvi.edu]
- Kidney Failure
Fatigue and anemia from the progressive kidney failure are common problems. Medical description: A number of renal-retinal disorders have been reported and the nosology is not clear. [wohproject.org]
failure * Metabolic acidosis * Growth retardation * Renal salt wasting * Tapetoretinal degeneration * Retinitis pigmentosa Causes - Senior Loken Syndrome Not supplied. [checkorphan.org]
Keywords: Chromosome Mapping, Chronic Kidney Failure, Consanguinity, Genetic Markers, Haplotypes, Homozygote, Human Pair 1 Chromosomes, Lod Score, Microsatellite Repeats, Pedigree, Retinitis Pigmentosa, Software, Syndrome Source: American Journal of Human [edoc.mdc-berlin.de]
Some of these include: Excessive urination (polyuria) Inability to concentrate urine Renal salt wasting Thirst Kidney failure Arterial hypertension (high blood pressure) Anemia Metabolic acidosis Thickening of kidney filtration tissues Increased blood [disabilitycasereview.com]
Eventually the patient may have symptoms such as nausea, vomiting, weight loss, fatigue, anemia and ultimately kidney failure. [rarediseases.org]
The diagnosis of Senior Loken syndrome is based on the clinical presentation of retinopathy and chronic interstitial nephritis. A complete workup of the organs involved is recommended, consisting of renal evaluation (urinalysis, renal function tests, abdominal ultrasound) and ophthalmologic tests (visual acuity, color vision, fundoscopy, refraction defects, ocular movements, electroretinogram). The liver should be assessed by liver function tests and ultrasound to exclude hepatic fibrosis. In addition, a neurological examination is recommended in infants.
On ultrasonography, the kidneys may show an increase in the echogenicity of renal parenchyma, cysts in a poorly differentiated corticomedullary junction or medullary cysts. These findings may eventually progress to more notable cysts and atrophy of the kidneys. A normal ultrasound appearance is possible in juvenile nephronophthisis but the diagnosis cannot be ruled out if medullary cysts are absent at the time of presentation .
Genetic analysis is required to diagnose Senior Loken syndrome. The most common mutation in this disease is the deletion of the gene NPHP1. Nephronophthisis can be diagnosed by mutational screening and histological findings on renal biopsy. Mutations in nine genes are linked to retinal degeneration and mutated NPHP1 to NPHP13 genes result in nephronophthisis.
He had no family history of renal disease, hypertriglyceridemia or cholelithiasis. He presented to our center complaining of acute abdominal pain and vomiting. He had abdominal tenderness without guarding. [ncbi.nlm.nih.gov]
He had no family history of renal disease, hypertriglyceridemia or cholelithiasis. He had abdominal tenderness without guarding. Investigations revealed a lipase level of 3856 I U/l and an abdominal CT scan showed features of acute pancreatitis. [cags.org.ae]
- Blood Urea Nitrogen Increased
urea nitrogen * Increased blood creatinine level * Thickening of kidney filtration tissues * Endstage kidney disease * Polyuria * Enuresis * Inability to concentrate urine * Kidney failure * Metabolic acidosis * Growth retardation * Renal salt wasting [checkorphan.org]
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