Alport syndrome

This PPT is very helpful to all the faculty and medical student to increasing the knowledge of alport syndrome.

1. By;mr.jagdish sambad Msc.nursing , nephro -urology IKDRC COLLEGE OF NURSING ALPORT SYNDROME 10/22/2018

2. Synonyms of Alport Syndrome Hematuria-nephropathy deafness Hemorrhagic familial nephritis Hereditary deafness and nephropathy Hereditary nephritis Hereditary nephritis with sensory deafness 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

3. Subdivisions of Alport Syndrome Autosomal dominant alport syndrome (ADAS) Autosomal recessive alport syndrome (ARAS) Col4a3-related nephropathy Col4a4-related nephropathy Col4a5-related nephropathy X-linked alport syndrome (XLAS) 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

4. INTRODUCTION Alport’s syndrome is a disease of collagen that affect the kidney always, the ears usually, and the eyes often. Cecil alport described in the association of hereditary heamaturic nephritis with hearing loss in a family whose affected male member die in adolescence. Genetic advance have broadened the scope of the condition to include optical defects, platelets abnormalities, late onset of kidney failure & Normal hearing in some families. At lease 85% of kindreds have x-linked disease and the most or all of those cases result from a mutation of COL4A5, the gene located at xq22 that codes for the α 5 (iv). Autosomal recessive inheritance occurs in perhaps 15 % of cases, and autosomal dominant inheritance has been shown in a handful of cases. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

5. Affected Populations Alport syndrome is estimated to affect approximately 1 in 5,000-10,000 people in the general population in the United States, which means that approximately 30,000-60,000 people in the United States have the disorder. Alport syndrome is estimated to account for 3% of children with chronic kidney disease and 0.2% of adults with end-stage renal disease in the United States. In XLAS, males are affected more severely than females. In the autosomal forms of Alport syndrome, males and females are affected with equal severity. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

6. Definition of alport syndrome Alport syndrome is a x-linked autosomal recessive disease that damages the tiny blood vessels in kidneys . It can lead to kidney disease and kidney failure. It can also cause hearing loss and problems within the eyes.  Alport syndrome causes damage kidneys by attacking the glomeruli. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

7. JUVENILE AND ADULT FORMS The distinction between juvenile and adult forms is fundamental to the understanding of Alport's syndrome. Kidney failure tends to occur at a similar age in all male members in a kindred , but this age varies widely among kindreds. Uremia in male patients occurs in childhood or adolescence in some families and in adulthood in others. Forms with early onset of kidney failure in middle age are called adult type nephritis. Extra renal manifestation tend to be more prominent in the juvenile kindreds. Because boys in juvenile kindreds tend to be small and frequently arise from New mutations. Adult- type kindreds are typically much larger, and new mutations occurs infrequently. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

8. Classic Genetics In most kindreds, inheritance of Alport's is x-linked. This was suggested by classic pedigree analysis, strengthened by tight linkage to restriction –fragment length polymorphous. (RFLP) And proved by identification of mutation. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

9. Molecular Genetics Causative mutations of COL4A5, these coding for α 5 (iv), appears consistently in many kindreds. These mutations include deletion, point mutations and splicing errors. There is poor correlation between mutation type and the clinical phenotype but deletion and some splicing errors cause severe kidney disease and early hearing loss. Missense mutations may cause juvenile disease with hearing loss or adult disease with or without hearing loss. Deletion involving the 5 end of the adjacent COL4A6 gene occurs consistently in families with esophageal and genital leiomyomatosis. Homozygous and mixed heterozygous for mutation of the COL4A3 or COL4A4 gene develop autosomal receive Alport's syndrome. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

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13. Pathology In young children, results of light microscopy of the kidneys may be normal or near normal. Glomeruli with persisting fetal morphology may be seen. As disease progresses interstial and tubular forms cells, which arise for reasons that are unclear, may become quite prominent, although they can also be found in many other conditions. Eventually progressive glomerulosclerosis and interstial scaring develop. The result of routine immunofluorescence examination for immunoglobulin's and compliment components are negative but staining for the α 5(iv) chain may be informative . 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

14. Pathology cont.. The GBM is up to there times it's normal thickness, split into several irregular layers and frequently interspersed with numerous electron dense granule about 40nm in diameter. In Florid case of juvenile type of the disease, the basement membrane lamellae may branch and rejoin in a complex basket –weave pattern. Early in the development of lesion, thinking of the GBM may predominate or may be the only abnormality visible. The abnormalities in children or adolescents with adult type Alport's syndrome may be unimpressive or indistinguishable from those of TBMD (thin basement membrane disease) disease. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

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16. Pathophysiology Mutations in the COL4A3, COL4A1 and COL4A5 genes cause AS. These genes each provide instructions for making one component of protein called type IV collagen. So, mutations in these genes result in abnormalities of the type IV collagen in glomeruli… Which prevents the kidneys from properly filtering the blood and allows blood and protein to pass into the urine… Gradual scarring of the kidneys occurs… Leads to kidney failure… Develop different signs and symptoms… 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

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18. Clinical feature People with Alport syndrome always have kidney involvement. Many people with the disease also have deafness and abnormalities of the eyes, because the type IV collagen proteins are important to the normal structure and function of the cochlea and the eye. The hallmark of Alport syndrome is blood in the urine (hematuria). In boys with X-linked Alport syndrome hematuria first appears in early childhood, and their urine is always positive for blood. Over 90% of girls with X-linked Alport syndrome have hematuria, but it may be intermittent. Some girls who carry a mutation in the alpha-5 chain gene do not have blood in their urine. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

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20. Clinical feature-1 All boys and girls with autosomal recessive Alport syndrome have hematuria . Most people who carry a mutation in one copy of the alpha-3 or alpha-4 chain genes have hematuria, but some do not. The hematuria of Alport syndrome is usually microscopic, meaning it can only be detected with a microscope or a urine dipstick. Sometimes children with Alport syndrome have brown, pink or red urine (gross hematuria) for several days, associated with a cold or the flu. This gross hematuria eventually stops on its own. It can be frightening, but it is not harmful. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

21. Clinical feature-2 As boys with Alport syndrome get older, they begin to show additional signs of kidney disease, such as protein in the urine (proteinuria) and high blood pressure. These symptoms are often present by the time the boys are teen-agers. Girls with Alport syndrome usually do not have protein in the urine and high blood pressure until much later in life, but occasionally these symptoms appear in childhood or adolescence. Deafness is an important feature of Alport syndrome. About 80% of boys with the disease will develop deafness at some point in their lives, often by adolescence. Fortunately, hearing aids are usually very effective in boys with deafness caused by Alport syndrome. Girls with the disease may also develop deafness, but less frequently than boys, and usually later in life. The deafness of Alport syndrome is not improved by kidney transplantation. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

22. Clinical feature-3 About 15% of men with Alport syndrome have an abnormality in the shape of the lens called anterior lenticonus , which may cause problems with vision and lead to cataract formation. Some people with Alport syndrome have abnormal pigmentation of the retina, but this does not result in any abnormalities of vision. Recurrent corneal erosion is a painful eye problem that can occur in people with Alport syndrome. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

23. Diagnosis A diagnosis of Alport syndrome is suspected based upon identification of characteristic symptoms, a detailed patient history, and a thorough clinical evaluation. The likelihood of diagnosis increases in individuals with a family history of Alport syndrome, kidney failure without known cause, early hearing loss or hematuria. A variety of specialized tests can help to confirm a suspected diagnosis . History and physical examination RFT, Urine analysis Renal biopsy Molecular genetic testing. Hearing and vision test. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

24. Treatment Treatment may require the coordinated efforts of a team of specialists. Pediatricians, nephrologists, audiologists, ophthalmologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment. Genetic counseling is beneficial for affected individuals and their families. Psychosocial support for the entire family is essential as well . Currently, there is no specific treatment for Alport syndrome. The goal is to treat the symptoms and help slow the progression of kidney disease. This may include: ACE inhibitor or ARB medicines (medications to control high blood pressure) Diuretics (water pills) Limit sodium (salt) in your diet 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

25. ACE Inhibitor Medications known as angiotensin-converting enzyme (ACE) inhibitors have been used to treat individuals with Alport syndrome. This off-label use may not be appropriate for all affected individuals and several factors must be considered before starting the therapy such as baseline kidney function, family history, and specific symptoms present. ACE inhibitors may be given when elevated levels of protein are detectable in the urine (overt proteinuria) in certain cases. These drugs are blood pressure medications that prevent (inhibit) an enzyme in the body from producing angiotensin II. Angiotensin II is a chemical that acts to narrow blood vessels and can raise blood pressure. ACE inhibitors in individuals with Alport syndrome have been shown to reduce proteinuria and slow the progression of kidney disease, delaying the onset of renal failure. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

26. Cont.. Although treatment may slow the progression of kidney disease in Alport syndrome, there is no cure for the disorder and no treatment that can completely stop kidney decline. The rate of progression of kidney decline in individuals with Alport syndrome is highly variable. In most affected individuals, kidney function eventually deteriorates to the point where dialysis or a kidney transplant is required . Dialysis is a procedure in which a machine is used to perform some of the functions of the kidney — filtering waste products from the bloodstream, helping to control blood pressure, and helping to maintain proper levels of essential chemicals such as potassium. End-stage renal disease is not reversible so individuals will require lifelong dialysis treatment or a kidney transplant. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

27. Cont.. A kidney transplant is preferred for individuals with Alport syndrome over dialysis and has generally been associated with excellent outcomes in treating affected individuals. Some individuals with Alport syndrome will require a kidney transplant in adolescence or the teen-age years, while others may not require a transplant until they are in their 40s or 50s. Most females with XLAS and some individuals will ADAS syndrome never require a transplant. If a kidney transplant is indicated, great care must be taken in selecting living related kidney donors to ensure that affected individuals are not chosen. Alport syndrome does not recur in kidney transplants. However about 3% of transplanted Alport patients make antibodies to the normal collagen IV proteins in the transplanted kidney, causing severe inflammation of the transplant (anti-GBM nephritis). 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

28. Nursing management 1. Impaired renal filtration related to glomerulonephritis and irregular formation of the glomerular basement membrane as evidenced by haematuria and proteinuria. 2. Impaired visual and auditory function related to type IV collagen mutations as evidenced by loss of hearing and myopia. 3. Fluid and electrolytes imbalance related to diarrhoea and haematuria . 4. Decreased in quality of life related to impaired visual and auditory functioning. 5. Risk for fluid volume excess related to swelling in legs, feet and around the eyes. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

29. Cont.. 6. Ineffective self care related to disease condition. 7. Altered nutrition: less than body requirement related to loss of appetite. 8. Anxiety related to long term disease condition. 9. Knowledge deficit related to disease condition, its causes, prognosis and its management. 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

30. Goal of nursing management Reduction of oedema Nutrition Administering medication Skin care Infection prevention Promoting psychological growth Parent teaching 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

31. Health education on diet Foods to eat with AS, High quality protein Foods with anti-oxidant property Food or drinks with diuretic property Foods rich in omega-3 fatty acid 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

32. DO NOT TAKE Foods not to eat with AS, High-sodium foods High-potassium foods Low-quality protein High-phosphorus foods Alcohol or caffeine containing drinks 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

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34. Compilation Cataract Sensorial hearing loss Chronic renal failure Depression Complication during pregnancy 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG

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36. Thank you… 10/22/2018 MR.JG SAMBAD,IKDRC COLLEGE OF NURISNG